Chapter 6 Drugs and behavior


CHAPTER 6 DRUGS AND BEHAVIOR>>PROFESSOR: HI. AND WELCOME BACK TO PSYCH
300 BRAIN AND BEHAVIOR. WE’RE GOING TO BE TALKING ABOUT DRUGS AND
BEHAVIOR TODAY OR CHAPTER 6 IN YOUR TEXTBOOK. SO OUR DISCUSSION WILL BUILD ON WHAT WE COVERED
IN THE LAST TWO CHAPTERS TALKING ABOUT THE NEURON
AND THE SYNAPSE. AND HERE WE’LL BE TRYING TO INVESTIGATE OR COVER, DISCUSS,
HOW DRUGS COME IN TO INFLUENCE THE ACTION OF THE CENTRAL NERVOUS
SYSTEM AND FUNCTIONALLY WORKING AT THAT SYNAPSE. THEN WE’LL TALK ABOUT HOW WE CLASSIFY DRUGS
AND TALK ABOUT FOUR DIFFERENT TYPES OF CLASSES OF DRUGS
AND HOW THEIR MECHANISM OF ACTION OPERATES. THAT WILL GIVE YOU THE BASIS THEN TO START
WORKING ON OR INVESTIGATING YOUR SPECIFIC DRUG THAT
YOU WANT TO DO YOUR PROJECT ON, YOUR MECHANISM OF ACTION BLOG. SO AFTER YOU WATCH THIS CLASS, YOU HAVE A
BETTER IDEA OF WHAT WE MEAN BY MECHANISM OF ACTION. YOU CAN SELECT THE DRUG THAT YOU WANT TO DO YOUR BLOG BASED ON AND START
THAT PROCESS. AND THEN WHAT WE’LL CONCLUDE THIS LECTURE
WITH WE’LL BE TALKING ABOUT EXPERIENCE AND HOW REPEATED
ADMINISTRATION OF CERTAIN DRUGS CAN CHANGE AND CAN INFLUENCE HOW THEY
INFLUENCE BEHAVIOR EARLY IN EXPOSURE TO THE DRUG VERSUS AFTER MANY EXPOSURES
TO THE DRUG. AND SOME OF THE MECHANISMS OR PROCESSES THAT THEY CAN
BE OPERATING. SO LET’S GO AHEAD AND GET STARTED. FIRST OF ALL, WHEN WE ADMINISTER A DRUG, THERE’S SEVERAL DIFFERENT
ROUTES OR WAYS THAT IT CAN GET INTO THE BODY AND HAVE ITS EFFECT
ON BEHAVIOR. AND THESE DIFFERENT ROUTES OF ADMINISTRATION HAVE DIFFERENT
EFFECTS. AND THE BEST WAY TO KIND OF THINK ABOUT THIS IN TERMS
OF BARRIERS, THERE ARE BARRIERS TO GETTING THROUGH INTO THE CENTRAL
NERVOUS SYSTEM. SO WE CAN SEE HERE WE HAVE THESE DIFFERENT
ROUTES OF ADMINISTRATION. AN ORAL ROUTE OF ADMINISTRATION WOULD BE LIKE
TAKING AND SWALLOWING THE PILL. THIS ROUTE OF ADMINISTRATION HAS A LOT OF ISSUES. FIRST, THE DRUG HAS TO DIFFUSE INTO THE STOMACH
LINING AND THEN IT HAS TO GO INTO THE BLOOD VESSELS. FROM THE BLOOD VESSELS IT THEN HAS TO TRAVEL THROUGH THE CIRCULATORY
SYSTEM. AND THEN FROM THE CIRCULATORY SYSTEM, IT HAS TO GO THROUGH
THE BLOOD-BRAIN BARRIER AND THEN IT HAS TO THEN FROM THE BLOOD-BRAIN
BARRIER GET INTO THE NEURONS AND PASS PERFORMANCE. SO THERE’S A LOT OF BARRIERS. SO THIS ORAL ROUTE OF ADMINISTRATION IS GOOD
IN THAT MOST PEOPLE CAN TAKE A PILL. IT’S CHALLENGING IN THAT THERE IS A LOT OF LIMITATIONS OF GETTING THE DRUG INTO THE
CENTRAL NERVOUS SYSTEM. SO THE ORAL ROUTE OF ADMINISTRATION IS CONVENIENT. BECAUSE IT HAS TO GO INTO THE STOMACH THERE ARE ACIDS THERE SO
IT MAY BREAK DOWN QUICKLY. AND YOU MAY NEVER GET THE DRUG IN THERE. SO WHEN YOU’RE DEVELOPING THESE DRUGS, YOU HAVE TO APPRECIATE ALL OF
THE BARRIERS FOR THEM GETTING INTO AND IMPACTING THE FUNCTION OF
THE NERVOUS SYSTEM. TOPICAL DOESN’T HAVE TO DEAL WITH THOSE STOMACH
ACIDS OR THE PROCESSES AND THE DIGESTIVE TRACT. TOPICAL WOULD BE AS THOUGH YOU WERE TO PUT AN ADHESIVE STRIP ON THE SKIN. AND THAT CONTAINS A DRUG THAT HAS TO DIFFUSE INTO THE SKIN THROUGH
THE FATTY TISSUE, INTO THE CIRCULATORY SYSTEM AND HAVE ITS EFFECT
FROM THERE. SO IT STILL HAS TO MAKE IT THROUGH THE BLOOD-BRAIN BARRIER. AND WHAT WE’LL SEE IS SOME DRUGS ARE VERY
EFFECTIVE IN GETTING THROUGH THE BLOOD-BRAIN BARRIER. OTHER DRUGS ARE LESS EFFECTIVE IN GETTING THROUGH THE BLOOD-BRAIN
BARRIER. SO TOPICAL WE DON’T HAVE TO DEAL WITH THE GASTRIC JUICES,
ACIDS, TO THE DRUG. BUT YOU STILL HAVE TO DIFFUSE TO THE SKIN. ONE OF THE LIMITATIONS IS CERTAIN DRUGS CAN CAUSE IRRITATION TO THE
SKIN. AND SO THAT’S ONE LIMITATION. I GUESS A GOOD EXAMPLE OF THIS WOULD BE THE
NICOTINE PATCH THAT YOU CAN WEAR SO THE NICOTINE CAN
DIFFUSE THROUGH YOUR SKIN AND GET INTO THE CIRCULATORY SYSTEM AND THEN
HAVE ITS EFFECT ON THE CENTRAL NERVOUS SYSTEM. INTRAMUSCULAR. THIS IS WHERE YOU’RE GOING TO INJECT THE DRUG INTO THE MUSCLES. SO NOW YOU’VE KIND OF BYPASSED THE NEED TO DIFFUSE ACROSS THE SKIN AND YOU’RE INJECTING
IT DIRECTLY INTO THE MUSCLES. AND, THEREFORE, THERE’S FEWER BARRIERS FOR
THAT DRUG TO HAVE TO GET THROUGH. BUT IT’S GOING TO BE — HAVE TO DIFFUSE FROM
THE MUSCLE INTO THE CIRCULATORY SYSTEM. FROM THE CIRCULATORY SYSTEM, IT STILL HAS TO GO THROUGH THE BLOOD-BRAIN BARRIER. SO THIS WILL HAVE A MUCH LONGER RELEASE PATTERN THAN SOME OF THE
OTHER ONES THAT WE’RE GOING TO TALK ABOUT BECAUSE IT’S IN THE MUSCLE
TISSUE AND ITS DIFFUSED. NOW, INHALATION, SUCH AS SMOKING A CIGARETTE,
IS ANOTHER ROUTE OF ADMINISTRATION. HERE THE NICOTINE CAN GO DIRECTLY THROUGH THE BLOOD SUPPLY THAT ARE FOUND IN
THE LUNGS AND GET IN VERY QUICKLY. ONE OF THE OTHER ROUTES OF ADMINISTRATION
THAT’S AMAZINGLY FAST WOULD BE INTRAVENOUS. THIS IS INJECTING THE DRUG DIRECTLY INTO THE CIRCULATORY SYSTEM, SUCH AS IF YOU’RE
BEING PREPPED FOR SURGERY AND THEY NEED TO GIVE YOU AN ANESTHETIC, THEY’LL
EITHER DO IT THROUGH INHALATION OR THEY CAN GIVE YOU AN IV THAT
CONTAINS IT. SO IT HAS A VERY QUICK ONSET THROUGH INTRAVENOUS. AGAIN, REALLY THE ONLY BARRIER THERE IN INTRAVENOUS
IS GOING TO BE THE BLOOD-BRAIN BARRIER THAT’S
PREVENTING IT. OUR LAST ROUTE OF ADMINISTRATION IS INTRACEREBRAL. INTRACEREBRAL IS WHERE YOU SKIP THE BLOOD-BRAIN
BARRIER AND YOU’RE INJECTING IT DIRECTLY INTO THE BRAIN. ONE OCCASION WHERE THIS OCCURS IS IF SOMEONE HAS SOME TYPE OF INFECTION,
BACTERIAL INFECTION, INSIDE OF THE CENTRAL NERVOUS SYSTEM. AND TRYING TO GET DRUGS, ANTIBIOTICS INTO THE SYSTEM IS DIFFICULT. ANTIBIOTICS ARE VERY DIFFICULT TO GET PAST THE BLOOD-BRAIN BARRIER. AND SO ON RARE OCCASIONS WHERE THEY THINK IT MAY BE HELPFUL, THEY’LL DO DIRECT
INTRACEREBRAL INJECTIONS OF ANTIBIOTICS TO TRY TO TREAT AN INFECTION. SO THERE IS AN EXAMPLE OF WHERE THE BLOOD-BRAIN BARRIER IS CAUSING A PROBLEM, ALTHOUGH IT
DOES A LOT OF HELP. IT PROTECTS AND KEEPS A LOT OF DANGEROUS KINDS
OF THINGS OUT OF THE CENTRAL NERVOUS SYSTEM. THERE WE’RE TRYING TO TREAT THE INFECTION,
AND WE’LL NEED TO USE AN ANTIBIOTIC DIRECTED — INJECTED
DIRECTLY INTO THE BRAIN OR SKIPPING THE BLOOD-BRAIN BARRIER. NOW, THESE DIFFERENT ROUTES OF ADMINISTRATION
HAVE DIFFERENT EFFECTS ON THE TIME FRAME OR THE
WAY THE DRUG WILL ACTUALLY COME IN AND INCREASE IN THE CENTRAL NERVOUS
SYSTEM. AND WHAT WE CAN DO IN THIS GRAPH IS LOOK AT PLASMA LEVEL CONCENTRATIONS
OF, LET’S SAY, COCAINE. SO IF YOU’RE TO INJECT COCAINE DIRECTLY INTO
THE VEINS OR INTRAVENOUSLY, WE CAN SEE BY 60 MINUTES WE’D
HAVE A HIGH CONCENTRATION FROM WHAT WE SEE AT 0 PRIOR TO THE INJECTION
OF COCAINE WITHIN THE CENTRAL NERVOUS SYSTEM. AND IT VERY QUICKLY KIND OF TAPERS OFF. BUT WHAT ABOUT IF WE USE THOSE OTHER ROUTES
OF ADMINISTRATION WHERE THERE ARE MORE BARRIERS
WHERE IT HAS TO DIFFUSE THROUGH? SO INTRANASAL INHALATION THERE WHERE IT HAS
TO DIFFUSE INTO THE CIRCULATORY SYSTEM, WE DON’T GET THAT
IMMEDIATE INCREASE IN PLASMA LEVELS. BUT IT REMAINS FAIRLY STABLE. IT REMAINS FAIRLY CONSTANT AND THERE ISN’T THAT VERY QUICK DROP-OFF. SO THE WAY THE DRUG UNFOLDS THROUGH TIME, THE LEVELS CAN VARY DEPENDING
ON THE ROUTE OF ADMINISTRATION. NOW, ORAL TAKING AND INGESTING COCAINE ORALLY,
WE SEE THAT THAT IS GOING TO TRANSLATE INTO A MUCH
LOWER PEAK INITIALLY AND THEN IT WILL GRADUALLY INCREASE AND THEN DECREASE
OVER TIME SO WE’RE NOT HAVING AS MUCH COCAINE WITH THAT OR ROUTE
OF ADMINISTRATION THAT WE WOULD HAVE WITH INTRANASAL OR INTRAVENOUS. AND WE SEE THE TEMPORAL CHARACTERISTICS OR HOW THE DRUG CAN IMPACT
THE CENTRAL NERVOUS SYSTEM VARIES DEPENDING ON THE ROUTE OF ADMINISTRATION. AND WE’LL COME BACK TO THIS IDEA THAT A ROUTE
OF ADMINISTRATION CAN ACTUALLY BE A USEFUL TOOL
IN TREATING DRUG ADDICTION AND UNDERSTANDING DRUG ADDICTION PROCESSES. BUT HERE THIS IS JUST ILLUSTRATING WHAT HAPPENS — WHAT WOULD IT
LOOK LIKE, THE BLOOD LEVELS, IF WE INJECTED SOMEONE DIRECTLY WITH COCAINE
INTRAVENOUSLY OR GIVE THEM INTRANASAL EXPOSURE OR ORAL EXPOSURE TO COCAINE. AND YOU CAN SEE YOU CAN GET A VERY QUICK INCREASE IN COCAINE IF
WE DO IV. BUT THEN THAT IS ELIMINATED FAIRLY QUICKLY. WHEREAS THESE OTHER ROUTES OF ADMINISTRATION WHERE THERE ARE MORE BARRIERS,
YOU DON’T GET THAT IMMEDIATE INCREASE BUT THEY TEND TO BE MORE
PROTRACTED OR THEIR LEVELS CONTINUE FOR A LONGER TIME FRAME. SO LET’S TALK ABOUT ANOTHER ASPECT OF THE
BLOOD-BRAIN BARRIER. AND WHAT WE SEE IS THAT IT’S NOT ALWAYS SO
PRESENT ACROSS THE ENTIRE CENTRAL NERVOUS SYSTEM. THERE IS ACTUALLY THREE PLACES IN THE CENTRAL NERVOUS SYSTEM WHERE THERE’S A WEAKNESS
OR THERE’S A LIMITATION OR THE BLOOD-BRAIN BARRIER ISN’T AS EFFECTIVE
IN GETTING — HAVING — PREVENTING CHEMICALS FROM GETTING INTO THE
CENTRAL NERVOUS SYSTEM. THE FIRST AREA THAT WE SEE WHERE THERE’S A
LIMITATION OR A WEAKNESS IN THE BLOOD-BRAIN BARRIER IS
THAT PITUITARY GLAND, AS WE CAN SEE HERE. AND IF YOU REMEMBER OUR DISCUSSION OF THE
NEUROANATOMY, THE PITUITARY GLAND IS ON THE MIDLINE, AND
IT’S INVOLVED IN — AND IT’S JUST BELOW THE HYPOTHALAMUS. IT’S INVOLVED IN — SO HERE IS THE PITUITARY. HERE IS THE HYPOTHALAMUS. IT’S INVOLVED IN REGULATING A NUMBER OF HORMONES THROUGHOUT THE CENTRAL
NERVOUS SYSTEM. SO WE CAN SEE THAT PART OF THAT ACTIVATION
ON THE DIFFERENT KINDS OF REGULATORY BEHAVIORS DEPEND
ON THE PITUITARY, AND IT NEEDS TO HAVE ACCESS TO THE CIRCULATORY SYSTEM
TO RELEASE CERTAIN TYPES OF HORMONES INTO THE SYSTEM. SO THAT MAKES SENSE THAT WE DON’T WANT A STRONG BLOOD-BRAIN BARRIER THERE. THE PINEAL GLAND IS RESPONSIVE TO THE EFFECTS
OF CERTAIN CHEMICALS THAT CHANGE, OF COURSE,
ACROSS THE COURSE OF THE DAY. AND IN OUR LAST CHAPTER WHEN WE WERE TALKING
ABOUT SLEEP, WE’LL SEE THAT MELATONIN LEVELS CAN INCREASE AND DECREASE. AND THEY HAVE THEIR EFFECTS ON OUR SLEEP-WAKE CYCLE. AND THEY NEED TO HAVE A NICE ACCESS TO THE CIRCULATORY SYSTEM. AND THOSE COMPOUNDS DON’T READILY MOVE THROUGH THE BLOOD-BRAIN BARRIER. SO BY WEAKENING IT THERE IN THE PINEAL GLAND, WE CAN ALLOW THEM TO HAVE ACCESS
AND INFLUENCE OUR CIRCADIAN RHYTHM OR WHEN WE WAKE UP AT A CERTAIN
TIME OF DAY AND GO TO SLEEP AT A CERTAIN TIME OF DAY ALLOWS ACCESS
THERE. NOW, THERE’S ONE LAST PLACE THAT HAS A WEAKENED BLOOD-BRAIN BARRIER, AND THAT IS THE AREA
POSTREMA. AND IF TOXIC SUBSTANCE THAT’S PASS THROUGH THERE START
TO ACTIVATE THAT AREA. WHAT’S INTERESTING IS IT INDUCES VOMITING. SO IT’S KIND OF LIKE A SAFETY SWITCH THAT IF YOU’RE EATING SOMETHING
THAT IS ABLE TO PASS THROUGH THAT THAT IS GOING TO BE TOXIC, WHAT
HAPPENS IS YOU START TO THROW UP. AND SO IT’S A LITTLE BIT OF A SAFETY
PROTECTION MECHANISM TRYING TO GET THOSE TOXINS OUT OF THE SYSTEM. AND IT’S A FIRST LINE OF DEFENSE AGAINST THAT. SO JUST HAVING A WEAKNESS RIGHT THERE, THAT MEANS SOME OF THOSE CHEMICALS CAN START TO
GET IN. AND IF YOU START THROWING UP, YOU CAN ELIMINATE VOMITING OR
YOU CAN ELIMINATE THAT CHEMICAL FROM THE SYSTEM AND PREVENT FURTHER
DAMAGE TO THE BODY AND THE BRAIN. NOW, ONCE THE DRUG GETS THROUGH THE BLOOD-BRAIN BARRIER OR STARTS TO INFLUENCE THE BRAIN,
WE SEE THAT IT CAN FUNCTION IN TWO WAYS. EITHER IT CAN FUNCTION AS AN AGONIST. FUNCTION AS AN AGONIST. AND THE DEFINITION OF AN AGONIST IS ANY DRUG
THAT INCREASES THE EFFECTIVENESS OF NEUROTRANSMISSION. NOW, THIS SEEMS LIKE A PRETTY STRAIGHTFORWARD DEFINITION, AND ON THE SURFACE IT IS. THAT WE’RE INCREASING THE FUNCTION OF THE DRUG OR THE NEUROTRANSMITTER
— THE DRUG IS INCREASING THE EFFECTIVENESS OF NEUROTRANSMISSION. WE’LL SEE THAT THAT CAN HAVE AN AMAZING VARIETY OR A GREAT DEAL OF EFFECTS
ON BEHAVIOR. SO YOU SEE AN AGONIST. YOU MIGHT THINK RIGHT NOW BASED ON A DEFINITION, OH, THAT’S ALL OF THE
GOOD DRUGS ARE AGONISTS BECAUSE THEY INCREASE NEUROTRANSMISSION. WE’LL SEE THAT SOME DRUGS THAT ARE USED THERAPEUTICALLY ARE AGONISTS. BUT OTHER DRUGS COULD BE POISONOUS OR AGONISTS. SO WE’LL SEE THAT THERE’S A WHOLE RANGE OF DRUGS THAT FUNCTION BY INCREASING NEUROTRANSMISSION
OR WHAT WE CONSIDER AGONIST. THE OTHER CLASS OF DRUGS ARE ANTAGONISTS. AND THAT’S A DRUG THAT DECREASES THE EFFECTIVENESS OF
NEUROTRANSMISSION. THEY PREVENT, HAMPER, INTERFERE WITH, CONTINUATE
NEUROTRANSMISSION. THAT’S AN ANTAGONIST. AND WHAT WE’LL SEE IS THEY CAN WORK AT MANY
DIFFERENT POINTS AND THOSE STAGES OF NEUROTRANSMISSION
WE TALKED ABOUT LAST CHAPTER AND THE SYNAPSE, OR COMMUNICATION
ACROSS THE SYNAPSE. SO WE CAN SEE THAT WITHIN SYNTHESIS, WE CAN
HAVE DRUGS THAT EITHER SERVE AS A PRECURSOR, SO THEY
WOULD BE AN AGONIST, OR DRUGS THAT INHIBIT THE SYNTHESIS OF NEUROTRANSMISSION. SO THOSE WOULD BE AN EXAMPLE OF AN AGONIST OR ANTAGONIST AT THE
SYNTHESIS PHASE OF NEUROTRANSMISSION. SO AN AGONIST WOULD HELP OR FACILITATE NEUROTRANSMISSION PRODUCTION, SYNTHESIS, OF
A NEUROTRANSMITTER. AND WE’LL GIVE YOU SPECIFIC EXAMPLES OF THESE
AFTER WE GO THROUGH ALL OF THESE DIFFERENT STAGES. NOW, REMEMBER, WE HAVE TO STORE THE NEUROTRANSMITTERS. AND A DRUG THAT INTERFERES WITH THAT STORAGE
WOULD BE AN ANTAGONIST. SO A DRUG THAT WOULD INHIBIT OR CAUSE THESE
VESICLES HERE TO BECOME LEAKY, WHICH THERE ARE DRUGS THAT DO THIS. THEY CAUSE THE VESICLES TO BE LEAKY. THE NEUROTRANSMITTER LEAKS OUT AND THEN IT’S
BROKEN DOWN BY ENZYMES WITHIN THIS AREA OF THE PRESYNAPTIC
MEMBRANE HERE OF THIS NEURON. IF IT BECOMES LEAKY, THEN THEY BREAK DOWN. AND NOW THAT NEUROTRANSMITTER IS NO LONGER GOING TO BE
ABLE TO HAVE ITS EFFECT. THAT WOULD BE AN EXAMPLE OF AN ANTAGONIST. SOMETHING THAT PREVENTS THE STORAGE. NOW RELEASE. WE HAVE DRUGS THAT FUNCTION TO EITHER HELP THE RELEASE OF THE NEUROTRANSMITTER,
FACILITATING NEUROTRANSMISSION WOULD BE CONSIDERED AN ANTAGONIST. WE ALSO HAVE DRUGS THAT PREVENT THE RELEASE OF NEUROTRANSMISSION
OR THEY SLOW DOWN. SO NOW THE NEUROTRANSMITTER IS NOT GOING TO
BE RELEASED AS EFFECTIVELY AND THOSE WOULD BE CONSIDERED ANTAGONISTS. SO RELEASE IS ANOTHER STAGE OF NEUROTRANSMISSION WHERE A DRUG CAN EITHER
FACILITATE, IMPROVE, ENHANCE AND ACT AS AN AGONIST, OR A DRUG COULD
CONTINUATE, HAMPER, PREVENT, RELEASE AND ACT AS AN ANTAGONIST. NOW, THE RECEPTOR INTERACTION, THIS IS WHERE
THERE’S A VARIETY OF WAYS THAT A DRUG CAN HAVE AN EFFECT. WHAT WE CAN SEE IS THAT WE HAVE AGONIST AND ANTAGONIST THAT FUNCTION
AT THE RECEPTOR. BUT THEY CAN BE A LITTLE BIT MORE COMPLEX AND
THAT THERE CAN BE, AS YOU SEE IN THIS PICTURE, SEVERAL BINDING SITES, PLACES
WHERE THE NEUROTRANSMITTER CAN BIND HERE OR HERE. SO IF A DRUG BINDS AND IT FACILITATES RECEPTOR
ACTION, IT’S AN AGONIST. IF IT BINDS AND PREVENTS THE FUNCTION OF THAT CHANNEL, IT’S AN ANTAGONIST. SO ACTIVATING THAT AND CAUSING THAT CHANNEL TO FUNCTION BETTER OR MORE THAN NORMAL
WOULD BE AN AGONIST. BINDING AND PREVENTING THAT ACTION WOULD BE
AN ANTAGONIST. AND WE’LL TALK MORE ABOUT THOSE WHEN WE GET INTO OUR
SPECIFIC EXAMPLES IN TERMS OF THAT. BUT KNOW THAT WE CAN HAVE THIS EFFECT — DRUGS
CAN IMPACT THE FUNCTION OF RECEPTORS IN EITHER
HELPING THOSE RECEPTORS WORK BETTER OR ACTUALLY FUNCTIONING LIKE THE NEUROTRANSMITTER
ITSELF. OR IT CAN PREVENT THE NEUROTRANSMITTER FROM BINDING
TO THAT LOCATION. A DRUG THAT FACILITATES BINDING IS AN AGONIST OR
HELPS BINDING IS AN AGONIST. WHEREAS A DRUG THAT PREVENTS BINDING OR PREVENTS
ACTION ON THE CHANNEL IS AN ANTAGONIST. NOW, INACTIVATION IS ANOTHER WAY IN TERMS
OF THIS. AND THIS COULD BE AS SIMPLE AS PREVENTING
THE ENZYMES THAT ARE PRESENT IN THE SYNAPTIC CLEFT FROM WORKING. SO AN ENZYME THAT NORMALLY BREAKS DOWN THAT NEUROTRANSMITTER IS INACTIVATED,
THAT WOULD BE AN AGONIST, BECAUSE YOU WOULD ESSENTIALLY HAVE MORE NEUROTRANSMITTER
THAN YOU NORMALLY WOULD IN THE SYNAPTIC CLEFT. SO HERE WE SEE GIVING A DRUG THAT PREVENTS
THOSE ENZYMES FROM BREAKING DOWN THE DRUGS SINCE
WE INCREASED THE AMOUNT OF THAT NEUROTRANSMITTER AND THEN INCREASED NEUROTRANSMISSION,
IT WOULD BE FUNCTIONING AS AN AGONIST. AND REUPTAKE. ANOTHER WAY THAT WE INACTIVATE THE DRUGS IS WHERE THE NEUROTRANSMITTERS NORMALLY
REABSORB PRESYNAPTICALLY, THERE’S DRUGS THAT PREVENT THAT REABSORPTION
OR REUPTAKE. AND THOSE THAT WOULD PROVIDE A SITUATION WHERE THERE
WOULD BE MORE NEUROTRANSMITTER IN THE SYNAPTIC CLEFT. AND THAT WOULD ENHANCE NEUROTRANSMISSION. SO ANYTHING THAT PREVENTS REUPTAKE WOULD BE
AN AGONIST. IT WOULD BE HELPING THEM IN THAT REGARD. AND THEN, FINALLY, YOU CAN HAVE DRUGS THAT
INFLUENCE THE BREAKDOWN OF THE NEUROTRANSMITTER WITHIN
THE PRESYNAPTIC MEMBRANE OR THE NEURON THERE. AND THOSE DRUGS WOULD — IF YOU INTERFERE
WITH THE DEGRADATION OR THE BREAK DOWN OF THAT
WOULD ESSENTIALLY INCREASE THE AMOUNT OF THAT NEUROTRANSMITTER AVAILABLE
TO BE RELEASED. AND THAT WOULD ALSO SERVE AS AN AGONIST. SO YOU CAN SEE AGONIST AND ANTAGONIST CAN
HAVE THEIR IMPACTS IN THESE VERY DIFFERENT STAGES OF
NEUROTRANSMISSION FROM THE SYNTHESIS TO THE STORAGE TO THE RELEASE, RECEPTOR,
ACTIVATION, INACTIVATING THE DRUG IN THE SYNAPSE BY TURNING
OFF THESE ENZYMES OR PREVENTING REUPTAKE OR EVEN WITHIN THE REABSORBED
NEUROTRANSMITTER WHAT WE’LL SEE IS THAT THESE DRUGS OR THESE NEUROTRANSMITTERS
CAN INCREASE OR DECREASE NEUROTRANSMISSION, DEPENDING ON
WHERE THEY’RE AT AND THEIR EFFECTS. SO THERE’S A LOT OF PLACES THAT PHARMACEUTICAL COMPANIES CAN LOOK TO TRY TO ENHANCE OR PREVENT
NEUROTRANSMISSION TO ALLEVIATE DISORDERS LIKE DEPRESSION OR ANXIETY
OR SCHIZOPHRENIA. AND SO THAT’S WHAT WE’LL SEE AS WE START TO MOVE
THROUGH OUR EXAMPLES WHERE RESEARCHERS HAVE TRIED TO USE THESE DIFFERENT
POINTS OF NEUROTRANSMISSION. SO WE TALKED ABOUT THIS AT A VERY GENERAL
LEVEL. LET’S GO IN AND TALK ABOUT THE SPECIFICS AND
GIVE YOU SOME EXAMPLE DRUGS AND HOW THEY CAN FUNCTION AS AN AGONIST
OR ANTAGONIST AND THESE DIFFERENT STAGES OF NEUROTRANSMISSION. FIRST, A GOOD EXAMPLE IS ACETYLCHOLINE. NOW, YOU MIGHT RECALL FROM OUR LAST CHAPTER WE TALKED
ABOUT THE DISCOVERY ACETYLCHOLINE WAS THE FIRST NEUROTRANSMITTER
THAT WAS DISCOVERED BY OTTO LOEWI. AND A LOT OF WORK HAS BEEN DONE SINCE. AND WHAT WE FIND IS THAT YOU CAN INCREASE LEVELS OF ACETYLCHOLINE,
WHICH IS A NEUROTRANSMITTER THAT IS IMPORTANT FOR LEARNING,
MEMORY, MOVEMENT. SO IT’S WIDELY USED THROUGHOUT THE CENTRAL NERVOUS
SYSTEM. WE’LL SEE WHEN WE TALK ABOUT THIS LATER IT’S
ALSO IMPORTANT FOR MEMORY, SPECIFICALLY WE’LL TALK
ABOUT ALZHEIMER’S DISEASE. BUT WE CAN INCREASE THE AMOUNT OF ACETYLCHOLINE
BY HAVING A DIET RICH IN SOME OF THOSE PRECURSOR CHEMICALS. SO BY INCREASING, FOR EXAMPLE, OLIVE OIL OR EGG YOLKS, WE CAN INCREASE
THE AMOUNT OF ACETYLCHOLINE PRECURSORS. AND IF THERE’S MORE OF THOSE AVAILABLE, THAT MEANS A CHOLINE-RICH DIET INCREASES THE LEVEL
OF ACETYLCHOLINE TO GO AROUND. SO THAT DIET WOULD ESSENTIALLY SERVE AS AN
AGONIST. SO, AGAIN, SYNTHESIS PROVIDING FROM YOUR DIET
MORE OF THE BASIC BUILDING BLOCKS THAT BUILD THAT WOULD FUNCTION AS AN
AGONIST. NOW, WHAT WE CAN SEE IS THAT THERE ARE CERTAIN
DRUGS OR COMPOUNDS THAT ACTUALLY CAN CAUSE THE RELEASE
OF — OR INFLUENCE THE RELEASE OF ACETYLCHOLINE. ONE OF THEM IS BLACK WIDOW SPIDER VENOM. AND YOU CAN IMAGINE THAT IF BLACK WIDOW SPIDER
VENOM CAUSES THE RELEASE OF ACETYLCHOLINE, IT’S GOING TO BE AN AGONIST. AND WHAT YOU WOULD EXPECT TO HAPPEN IS IF YOU’RE RELEASING, YOU’RE
FACILITATING, YOU’RE ENHANCING NEUROTRANSMISSION WITH THAT MUCH
MORE THAN YOU EXPECTED, YOU MIGHT EXPECT GIVEN OTTO LOEWI’S EXPERIMENT
THAT YOUR HEART RATE WOULD SLOW DOWN. YOU MIGHT ALSO EXPECT BECAUSE, REMEMBER, ACETYLCHOLINE HAS THAT DIFFERENT EFFECT ON SKELETAL MUSCLES
AND CARDIAC MUSCLES AND ACTUALLY CAUSES A PARALYSIS, A RIGID PARALYSIS. SO ALL OF THESE MUSCLES START TO CONTRACT. SO IF YOU’RE BITTEN BY A BLACK WIDOW SPIDER
OR AN INSECT IS, WHAT HAPPENS IS THE RESPIRATION,
THE HEART ACTUALLY STARTS TO SLOW DOWN. AND THEN ALL OF THE MUSCLES BECOME RIGID. THAT’S A VERY EFFICIENT TOOL FOR CAPTURING YOUR PREY. THEY’RE PARALYZED AND THE HEART STARTS TO SLOW DOWN. AND IT’S A VERY ADAPTIVE TOOL OR A GOOD TOOL TO ACTUALLY CATCH YOUR PREY. SO BLACK WIDOW SPIDER VENOM IS AN EXAMPLE
OF AN ACETYLCHOLINE AGONIST THAT FUNCTIONS TO PROMOTE
THE RELEASE OF ACETYLCHOLINE AT THE SYNAPSE. SO THAT’S WHAT IT DOES. IT STARTS DUMPING A BUNCH OF ACETYLCHOLINE INTO THE
SYNAPSE, AND IT’S GOING TO DO IT WHEREVER THE BLACK WIDOW SPIDER VENOM IS
APPLIED. IF IT’S ON CARDIAC TISSUE, THAT MEANS YOU’RE GOING TO
SLOW DOWN THE HEART RATE. AND IF IT’S APPLIED TO MUSCLE TISSUE, THE
MUSCLES ON BOTH SIDES OF THE ARM WILL START TO CONTRACT AND YOU’LL GET
THIS PARALYSIS. IT WILL BE A RIGID PARALYSIS WHERE THE ARM ISN’T ABLE TO
MOVE EITHER DIRECTION. BECAUSE BOTH MUSCLES ON EITHER SIDE OF THE
ARM ARE CONTRACTING VERY STRONG. NOW, BOTULIN TOXIN, OR BOTOX, THAT MAKES UP
BOTOX, WORKS IN THE OPPOSITE DIRECTION. IT PREVENTS THE RELEASE OF ACETYLCHOLINE AT THE SYNAPSE. AND SO THIS WILL ACTUALLY CAUSE MUSCLES TO RELAX. IF YOU’RE NOT RELEASING BOTULIN OR YOU’RE
NOT RELEASING ACETYLCHOLINE OR YOU’RE PREVENTING THE RELEASE
OF ACETYLCHOLINE, NOW THERE’S THE SYNAPSE THAT’S GOING UNUSED. AND IF YOU INJECT IT TO CERTAIN PARTS OF THE BODY, YOU CAN ACTUALLY
TAKE AND CAUSE THE MUSCLES TO RELAX. THERE ARE CERTAIN NEUROLOGICAL CONDITIONS,
SUCH AS SPASMODIC TORTICOLLIS WHERE YOU HAVE MUSCLES
THAT ARE SPONTANEOUSLY CONTRACTING BECAUSE OF THESE MOTOR NEURONS
ARE FIRING IN A RANDOM FASHION. AND SO ORIGINALLY BOTULIN TOXIN WAS DEVELOPED
TO TREAT THAT SPASMODIC TORTICOLLIS. BUT PEOPLE REALIZED IT COULD OFTEN BE USED
FOR COSMETIC PURPOSES AND INJECT IT INTO AREAS
WHERE WRINKLES ARE OCCURRING BECAUSE THESE MUSCLES ARE CONTRACTING. BUT THIS IS AN EXAMPLE OF ACETYLCHOLINE ANTAGONIST, AND IT PREVENTS THE RELEASE OF ACETYLCHOLINE. AND YOU CAN SEE THAT IT’S GOING TO HAVE VERY DIFFERENT EFFECTS,
DEPENDING ON WHERE IT’S APPLIED. AND IT’S BEEN USED TO TREAT NEUROLOGICAL DISORDERS
WHERE THE MOTOR NEURONS ARE FIRING TOO QUICKLY, OR COSMETIC
REASONS WHERE THERE MAY BE MORE MUSCLE CONTRACTION AND CAUSES
WRINKLES. SO THAT’S RELEASE. WE’VE TALKED ABOUT SYNTHESIS. WE’VE TALKED ABOUT RELEASE. WE CAN TALK ABOUT RECEPTOR ACTION. AND TWO GOOD EXAMPLES OF BOTH AN AGONIST AND AN ANTAGONIST ARE NICOTINE
AND CURARE. THAT MEANS THAT WHEN WE — IF WE WERE TO SMOKE A CIGARETTE
OR CHEW SOME TOBACCO, INGEST NICOTINE IN SOME FASHION, WEAR A NICOTINE
PATCH USING THAT DIFFERENT ROUTE OF ADMINISTRATION, WHAT’S
GOING TO HAPPEN IS THAT IT’S GOING TO BIND TO THOSE ACETYLCHOLINE RECEPTORS
AND FUNCTION MUCH LIKE ACETYLCHOLINE WOULD IN THAT RECEPTOR AND HAVING
IT’S EFFECT ON THE CHANNEL. NOW, IN THE PERIPHERAL NERVOUS SYSTEM, THAT
MAY INVOLVE INCREASED MUSCLE TONE. BUT IN THE CENTRAL NERVOUS SYSTEM, THAT MEANS YOU’RE GOING TO CHANGE THE COMMUNICATION
OR ENHANCE THE NEUROTRANSMISSION IN THE CENTRAL NERVOUS SYSTEM. SO SMOKING, THERE’S NICOTINE IN THERE, AND
THAT’S GOING TO ENHANCE COMMUNICATION IN THE ACETYLCHOLINE-BASED NEUROTRANSMISSION. THAT OFTEN TRANSLATES INTO INCREASED ATTENTION, INCREASED MEMORY. BUT, OF COURSE, SMOKING ITSELF HAS A LOT OF
OTHER TERRIBLE SIDE EFFECTS, SUCH AS CANCER IS A
BIG ONE. SO ENGAGING WITH THIS WHILE IT MAY HAVE SOME ENHANCING PROPERTIES,
IT ALSO HAS SOME SIGNIFICANT CHALLENGES OR BAD SIDE EFFECTS. NOW, CURARE, ON THE OTHER HAND, IS ACETYLCHOLINE ANTAGONIST. WHAT IT DOES IS IT BINDS AND PREVENTS — IT
ACTUALLY BINDS TO THE ACETYLCHOLINE RECEPTOR AND PREVENTS
THAT FROM ACTUALLY FUNCTIONING. SO IT KIND OF TURNS OFF ACETYLCHOLINE. SO YOU CAN IMAGINE THAT YOU’LL SEE, A, WITH THE CURARE,
CURARE HAS BEEN USED, WAS DISCOVERED AS A CHEMICAL BECAUSE IT WAS USED
TO HUNT. CERTAIN TRIBES IN AFRICA WOULD COAT THE TIPS OF THEIR DARTS,
AS YOU CAN SEE HERE, WITH CURARE, AND THEY WOULD THEN APPLY — USE THESE
DARTS AND INJECT — USE THEM TO CATCH PREY. IF YOU WERE TO INTRODUCE CURARE OR ABLE TO
HIT YOUR PREY, WHAT WOULD HAPPEN IS THAT THE MUSCLES
WOULD ALL RELAX AND THE HEART RATE WOULD START TO SPEED. JUST KIND OF THE OPPOSITE EFFECT OF WHAT WE SEE WITH BLACK WIDOW SPIDER VENOM. SO CURARE IS BINDING TO THE ACETYLCHOLINE RECEPTOR BUT PREVENTING ANY
KIND OF FUNCTION OF THAT. SO THEY WOULD BE CONSIDERED AN ANTAGONIST. SO YOU WANT TO KEEP THAT IN MIND THAT CURARE WOULD BE A GOOD ANTAGONIST
IN TERMS OF PARALYZING THE MUSCLES BY KEEPING THE HEART RUNNING FASTER. WHEN WE TALK ABOUT ANOTHER DRUG HERE IN A LITTLE BIT. SO OUR NEXT TYPE OF DRUG EFFECT WE CAN TALK
ABOUT IS INACTIVATION WITHIN THE ACETYLCHOLINE SYSTEM. AND ACETYLCHOLINE ESTERASE, ACETYLCHOLINE ESTERASE IS VERY IMPORTANT
FOR BREAKING DOWN ACETYLCHOLINE IN THE SYNAPSE. AND THAT IS AN ENZYME. AND WHAT WE FOUND IS THAT WITHIN THESE ENZYMES, WE CAN
ACTUALLY INFLUENCE OR CHANGE THEIR FUNCTION. AND SO WITH ACETYLCHOLINE ESTERASE, WE CAN
PERMANENTLY TURN THAT OFF WITH THE COMPOUND KNOWN AS SARIN
OR NERVE GAS. SARIN IS THE NAME OF THIS TYPE OF ORGANOPHOSPHATE THAT
WILL PERMANENTLY SHUT OFF ACETYLCHOLINE ESTERASE IN THE SYNAPTIC CLEFT. AND IF YOU DO THAT, WHAT HAPPENS IS THAT ACETYLCHOLINE WILL CONTINUE
TO BE RELEASED, BUT IT’S NEVER BROKEN DOWN. IT MAY DIFFUSE AWAY A LITTLE BIT. BUT IT JUST BUILDS UP. YOU’RE FLOODING THE SYNAPSE. AND SO WHAT YOU’LL SEE IN THAT SITUATION IS
THAT THE HEART WILL START TO SLOW DOWN. AND ALL THESE MUSCLES WILL BECOME VERY RIGID, MUCH LIKE WHAT YOU SEE WITH BLACK WIDOW
SPIDER VENOM CAUSING THE RELEASE OF THIS. BUT BECAUSE YOU DON’T HAVE ANY ACETYLCHOLINE
ESTERASE WORKING TO REMOVE IT, YOU’RE JUST FLOODING
THAT SYNAPSE. AND WHAT WE SEE IS THAT IS USED IN THIS NERVE GAS AGENT
LIKE SARIN. NOW, THIS IS REALLY A SPECTRUM HERE. SO ON THE ONE HAND WE HAVE SARIN THAT PERMANENTLY INACTIVATES
ACETYLCHOLINE ESTERASE, THIS ENZYME THAT BREAKS DOWN ACETYLCHOLINE. ON THE OTHER END OF THESE ORGANOPHOSPHATES THAT BLOCK INACTIVATION,
YOU HAVE ARICEPT. ARICEPT IS A DRUG USED TO TREAT ALZHEIMER’S DISEASE. AND IT MOMENTARILY BINDS OR INACTIVATES ACETYLCHOLINE SO THAT ALTHOUGH
THERE’S A REDUCTION IN ACETYLCHOLINE, IN ALZHEIMER’S IT TRANSLATES
TO THESE MEMORY PROBLEMS. WE CAN MOMENTARILY INCREASE ACETYLCHOLINE. NOT TO THE LEVEL WHERE YOU’RE GOING TO SEE THOSE RIGID
PARALYSIS OR THE SPEEDING — THE CHANGE IN THE HEART RATE OR SLOWING
DOWN OF THE HEART RATE LIKE YOU WOULD WITH SARIN GAS BECAUSE YOU’RE SHOWING
THIS INCREASE IN ACETYLCHOLINE. BUT WHAT YOU SEE WITH ARICEPT IS IT’S JUST
ABLE TO TEMPORARILY INCREASE THE AMOUNT OF ACETYLCHOLINE
SO THAT YOU’RE ABLE TO MAYBE REIGNITE SOME OF THAT NEUROTRANSMISSION
THAT IS STOPPED OR STALLED IN THESE INDIVIDUALS WITH ALZHEIMER’S
DISEASE. SO ON ONE END YOU HAVE SARIN GAS THAT PERMANENTLY TURNS OFF OR ELIMINATES ACETYLCHOLINE ESTRACE
FROM THE SYNAPSE CAUSING DEATH IN THESE INDIVIDUALS. ON THE OTHER HAND YOU HAVE ARICEPT, WHICH CAN BE USED TO TREAT ALZHEIMER’S DISEASE. IT’S NOT 100% EFFECTIVE AND IT DOES HELP SOMETIMES WITH PEOPLE. BUT IT’S DEFINITELY NOT A CURE FOR A LOT OF THE PROCESS THAT’S GOING ON. NOW, I KIND OF LAID OUT A COUPLE OF BREAD
CRUMBS HERE. LET’S SAY THAT YOU HAVE AN IMMEDIATE RESPONSE
TEAM AND SOMEBODY IS BEING, AS WE CAN SEE HERE, IMPACTED BY SARIN
GAS. IS THERE A DRUG OR A COMPOUND THAT YOU MIGHT WANT TO USE TO COMBAT
THAT SARIN GAS UNTIL IT CAN BE ELIMINATED FROM THE SYSTEM THAT WE’VE
ALREADY TALKED ABOUT? WHAT WOULD BE ONE DRUG THAT MIGHT BE EFFECTIVE
IN THAT? WELL, LOOK AT YOUR NOTES. IF WE LOOK BACK, MAYBE YOU WOULD SAY CURARE. AND CURARE WOULD BE GOOD. BECAUSE MAYBE WITH CURARE WHAT YOU COULD DO IS TEMPORARILY GIVE THAT
— BLOCK ACETYLCHOLINE’S EFFECT ON THOSE RECEPTORS AND THEN ALLOW FOR
SOME OF THAT SARIN TO BE REMOVED AND YOU COULD POTENTIALLY INTERVENE
AND PREVENT THAT EFFECT. SO YOU CAN START TO SEE THAT YOU CAN USE THESE
IN COMBINATION TO HAVE DIFFERENT EFFECTS. SO MOVING DO A DIFFERENT NEUROTRANSMITTER
SYSTEM THAT WE’LL TALK ABOUT, DOPAMINE IS NICE BECAUSE
THERE’S A VARIETY OF WAYS IN WHICH WE CAN CHANGE, EITHER HAVE DOPAMINE
AGONISTS OR ANTAGONISTS. L-DOPA IS A DRUG THAT WE SPOKE ABOUT THAT’S
OFTEN GIVEN TO PEOPLE WITH PARKINSON’S DISEASE. REMEMBER, PARKINSON’S DISEASE YOU HAVE A DEGENERATION OF THE SUBSTANTIA NIGRA. AND THOSE ARE DOPAMINERGIC-RICH NEURONS THAT PROJECT UP TO THE BASAL GANGLIA. AND BY GIVEN L-DOPA, YOU CAN INCREASE THE AMOUNT OF DOPAMINE AVAILABLE. AND WHAT WE’VE SEEN IS THAT THAT CAN HAVE
TEMPORARY EFFECTS OF ALLEVIATING SOME OF THOSE SYMPTOMS
ASSOCIATED WITH PARKINSON’S DISEASE. SO L-DOPA WOULD BE AN AGONIST. IT’S HELPING IN THE SYNTHESIS OR THE BIOCHEMICAL PATHWAY AND
THE SYNTHESIS OF DOPAMINE. NOW, IN TERMS OF REUPTAKE, BOTH COCAINE AND AMPHETAMINE CAN PREVENT REUPTAKE OF THE DOPAMINE. SO IF DOPAMINE IS NOT BEING REABSORBED PRESYNAPTICALLY OR INTO
THE RELEASING NEURON, THAT MEANS THERE’S MORE DOPAMINE TO GO AROUND AND
MORE BINDING. AND YOU CAN NOW HAVE THAT INCREASED AMOUNT OF DOPAMINE
AVAILABLE TO BIND AND ENHANCE NEUROTRANSMISSION. WHAT WE FIND IS THAT DOPAMINE IS LOCATED IN BOTH THESE MOTOR SYSTEMS LIKE WE SEE THE DAMAGE
IN PARKINSON’S DISEASE, BUT IT’S ALSO INVOLVED IN THE REWARD SYSTEMS. AND SO WHEN YOU’RE EATING THAT DELICIOUS CHOCOLATE BAR OR YOU
HAVE A REALLY GOOD MEAL AND ITS PLEASURABLE, PLEASURABLE CHARACTERISTICS,
WE’RE ACTIVATING DOPAMINERGIC SYSTEMS, AND COCAINE AND AMPHETAMINE
ARE FUNCTIONING TO INCREASE NEUROTRANSMISSION BY PREVENTING DOPAMINE
FROM BEING REABSORBED. INTERESTINGLY ENOUGH, WE SEE THAT AMPHETAMINE
ALSO CAUSES THE RELEASE, THE PRESYNAPTIC RELEASE
OF DOPAMINE. SO AMPHETAMINE WILL ACTUALLY CAUSE THE DOPAMINE
TRANSMITTERS TO RUN IN REVERSE, CAUSING DOPAMINE TO BE ACTIVELY RELEASED
FROM THE PRESYNAPTIC MEMBRANE. SO AMPHETAMINE IS DOING A LOT IN TERMS OF
AIDING NEUROTRANSMISSION, AND IT’S A STRONG AGONIST
OF THE DOPAMINERGIC SYSTEM INCREASING TRANSMISSION. NOW, AT THE RECEPTOR LEVEL, WE CAN SEE THAT CHLORPROMAZINE, WHICH IS A DRUG USED TO TREAT
SCHIZOPHRENIA, CAN BLOCK A DOPAMINE SITE AND ACTUALLY PREVENT IT FROM
HAVING AN EFFECT. AND SO WHAT WE CAN SEE IS THAT YOU HAVE DIFFERENT
SITES ON HERE. SO WE’LL SEE A D2 RECEPTOR INDICATING IT’S A SITE ON THIS
HERE, A DOPAMINE RECEPTOR SITE, AND THEN CHLORPROMAZINE IS AVAILABLE. IT WILL BLOCK DOPAMINE TRANSMISSION. SO WHAT WE SEE IS THAT CHLORPROMAZINE HAS
BEEN USED TO TREAT SCHIZOPHRENIA IN TERMS OF BLOCKING THE
DOPAMINE NEUROTRANSMISSION AND THE ROLE OF DOPAMINE AND SOME OF THOSE
SYMPTOMS ASSOCIATED WITH SCHIZOPHRENIA. SO THAT’S REALLY A LOT OF THE WAYS IN WHICH
DRUGS CAN IMPACT NEUROTRANSMISSION. I GAVE YOU SOME EXAMPLES THERE. NOW WHAT WE WANT TO DO IS GIVE YOU DIFFERENT CLASSES OF
DRUGS. AND THERE’S A LOT OF WAYS THAT WE COULD POTENTIALLY CLASSIFY
DRUGS. WE COULD TRY TO GO IN AND CLASSIFY THEM BASED
ON THEIR MECHANISM OF ACTION. HOW THEY INFLUENCE NEUROTRANSMISSION. WHERE THESE ALL DRUGS INFLUENCE RECEPTOR ACTIVATION
AND REACTIVATION. THESE ALL IMPACT THE SYNTHESIS. THESE IMPACT THE RELEASE. BUT BECAUSE DRUGS CAN HAVE SO MANY DIFFERENT
EFFECTS OF NEUROTRANSMISSION AND HAVE THE SAME EFFECT
ON BEHAVIOR WHERE YOU CAN SEE THAT TWO DRUGS CAN BE FUNCTIONING IN A
VERY SIMILAR WAY BUT CHANGE BEHAVIOR DRAMATICALLY, WE TEND TO CLASSIFY
DRUGS BASED ON THEIR NET EFFECT ON BEHAVIOR, NOT THEIR MECHANISM OF
ACTION. BUT IT’S IMPORTANT TO UNDERSTAND THEIR MECHANISM OF ACTION TO
TRY TO UNDERSTAND AND EXPLAIN WHY THEY INFLUENCE BEHAVIOR IN THE
WAY THAT THEY DO. SO OUR CLASSIFICATION SYSTEM WE’LL TALK ABOUT,
WE’LL TALK ABOUT HERE FOUR DIFFERENT TYPES OF DRUGS,
CLASSES OF DRUGS, AND GIVE YOU EXAMPLES OF EACH ONE. TALK ABOUT THESE DRUGS’ MECHANISM ON ACTION AND SOME POTENTIAL SIDE EFFECTS ASSOCIATED
WITH THEM. FIRST WE’LL TALK ABOUT ANTI-ANXIETY AGENTS
AND SEDATIVE HYPNOTICS. WE’LL TALK ABOUT WHAT THEY’RE USED FOR AND
WHAT’S THEIR MECHANISM OF ACTION AND SOME EFFECTS
THAT THEY HAVE. AND THEN WE’LL TALK ABOUT ANTIPSYCHOTIC AGENTS. AND THEN WE’LL TALK ABOUT ANTIPSYCHOTIC AGENTS USED TO TREAT, FOR EXAMPLE,
SCHIZOPHRENIA. AND WE’LL TALK ABOUT ANTIDEPRESSANTS AND WHAT
THEIR MECHANISM OF ACTION IS. AND THEN WE’LL TALK ABOUT OPIOID OR DRUGS
THAT ARE USED, ANALGESICS USED TO REDUCE PAIN. SO WITH OUR CLASSIFICATION SYSTEM, WE CAN
SEE THAT EVEN WITHIN THESE ANTI-ANXIETY AND SEDATIVE
HYPNOTICS, WE HAVE SEVERAL DIFFERENT EXAMPLES. FOR EXAMPLE, WITH SEDATIVES, WE SEE ALCOHOL
IS A GOOD EXAMPLE OF THAT. AND BARBITURATES ARE A GOOD EXAMPLE OF THAT. WHEREAS IN ANXIOLYTIC, WE HAVE VALIUM WHICH
IS AN EXAMPLE OF A DRUG THAT FUNCTIONS TO REDUCE ANXIETY. SO WE HAVE SEDATIVES AND ANXIOLYTICS OR AGENTS THAT FUNCTION TO REDUCE ANXIETY,
AND VALIUM IS AN EXAMPLE. AND WE CAN USE THEM TO EITHER MOMENTARILY
SEDATE PEOPLE WHO ARE IN AN EXTREMELY AROUSED OR
STRESSED CONDITION AND CAN BE PRESCRIBED BARBITURATES. OR DRUGS CAN BE PRESCRIBED FOR PEOPLE WHO SUFFER FROM ANXIETY, SEVERE ANXIETY AND TRYING
TO REDUCE SOME OF THEM EXPERIENCING THEIR ANXIETY. SO WHAT IS THEIR MECHANISM OF ACTION. AND THIS IS REALLY IMPORTANT. WHAT WE SEE IS THAT THESE ANTI-ANXIETY AGENTS
AND SEDATIVE HYPNOTICS ARE FUNCTIONING THROUGH
THE GABAergic NEUROTRANSMITTER SYSTEM. SO GABA IS A NEUROTRANSMITTER. AND IT IS A MAJOR INHIBITORY NEUROTRANSMITTER IN THE CENTRAL
NERVOUS SYSTEM. SO WHAT HAPPENS IS YOU HAVE A GABA RECEPTOR,
AND IT’S ASSOCIATED WITH THIS CHANNEL. AND WHAT WE SEE IS THAT ONCE THIS CHANNEL OPENS UP, CHLORIDE — WE TALKED ABOUT
THOSE IONS BEFORE, SODIUM CHLORIDE IS THE HIGHEST CONCENTRATION OUTSIDE
OF THE CENTRAL NERVOUS SYSTEM. AND WE DIDN’T REALLY GO INTO MUCH DETAIL ABOUT
THOSE CHLORIDE IONS. BUT THOSE CHLORIDE IONS ARE NEGATIVELY CHARGED. AND WE HAVE CHLORIDE CHANNELS IN THE CENTRAL
NERVOUS SYSTEM. AND GABA WHEN IT BINDS WHAT HAPPENS IS GABA
BINDS AND IT WILL ALLOW CHLORIDE IONS TO FLOW IN THAT ARE NEGATIVELY
CHARGED AND THEY WILL INHIBIT ACTION POTENTIALS, BASICALLY
SHUTTING DOWN THE CENTRAL NERVOUS SYSTEM. SO THEY CAN TURN OFF THE NERVOUS SYSTEM IF
GABA BINDS. NOW, SEDATIVE HYPNOTICS — SO THERE’S A PLACE
WHERE A GABA NEUROTRANSMITTER WILL BIND, AND IT WILL
PREVENT THE NEURON ARE FIRING BY ALLOWING CHLORIDE TO FLOW INTO THE
NEURON AND PRODUCING THESE IPSPs OR BASICALLY SHUTTING DOWN THE NEURON. WELL, THE SEDATIVE HYPNOTIC SITE, AS WE CAN
SEE HERE, IS WHERE ALCOHOL OR BARBITURATES BIND. AND THEY CAN ALSO COMPLETELY TURN OFF — THEY CAN TURN OFF OR FUNCTION
JUST LIKE GABA WHERE THEY’LL PREVENT OTHER ACTION POTENTIAL FROM FIRING. SO THEY CAN — THEY BIND THEMSELVES TAKING ALCOHOL OR BARBITURATES
CAN TURN OFF THOSE NEURONS. NOW, THERE’S ANOTHER SITE AT THE GABA RECEPTOR
HERE WHERE BENZODIAZEPINES OR DRUGS THAT FUNCTION
TO REDUCE ANXIETY CAN BIND. NOW, WHAT’S INTERESTING IS THAT THESE BENZODIAZEPINES
DEPEND ON GABA BEING AVAILABLE. SO HERE WHAT WE HAVE IS GABA HAS TO BE PRESENT FOR BENZODIAZEPINES TO HAVE AN EFFECT. THESE ARE CALLED INDIRECT AGONISTS. SO WHILE ALCOHOL OR BARBITURATES ARE DIRECT
AGONISTS IN THAT THEY CAN ALL ON THEIR OWN FUNCTION TO CAUSE
THIS CHANNEL, BENZODIAZEPINES BASICALLY HELP GABA. SO THEY’RE INDIRECT AGONISTS IN TERMS OF HELPING GABA TO HAVE ITS EFFECT HERE. SO THEY MIGHT DO SOMETHING WHERE THEY CAUSE GABA TO STAY BOUND
A LITTLE BIT LONGER. NOW, HERE IS WHAT’S IMPORTANT TO TAKE AWAY
FROM THIS CLASS OF DRUGS HERE IS THAT IF YOU WERE TAKING
SOMETHING, A BENZODIAZEPINE FOR AN ANXIETY DISORDER AND
THEN YOU START TO DRINK ALCOHOL, WHAT’S GOING TO HAPPEN IS YOU’RE
GOING TO HAVE ALL THREE OF THESE. AND GABA IS PRESENT, SO BENZODIAZEPINE IS
KEEPING GABA PRESENT, AND YOU’RE DRINKING ALCOHOL, THAT MEANS YOU
CAN COMPLETELY SHUT DOWN THIS SYSTEM FOR MUCH LONGER THAN WHAT SHOULD
BE. AND THIS COMBINATION OF ALCOHOL WITH THOSE BENZODIAZEPINES ARE OFTEN DEADLY. PEOPLE EASILY OVERDOSE. AND YOU HEAR ABOUT THIS IN THE MEDIA HOW PEOPLE THAT
ARE TAKING ANTI-ANXIETY AGENTS AND THEY START DRINKING ALCOHOL AND
THE COMBINATION OF BOTH OF THESE ARE DEADLY. SO YOU DON’T WANT TO COMBINE THESE TWO AGENTS TOGETHER. THIS IS VERY, VERY DANGEROUS TO KEEP IN MIND. WE SEE THERE ARE ALSO SOME OTHER COMPLICATIONS
FROM THIS CLASS OF DRUGS. FIRST AND FOREMOST IS ALCOHOL CONSUMED WHILE SOMEONE IS PREGNANT CAN HAVE VERY DAMAGING
EFFECTS ON THE DEVELOPMENT OF THE FETUS. AND SO YOU CAN SEE THAT IF SOMEONE DOES DRINK
WHEN THEY’RE PREGNANT, THEY WILL DEVELOP FETAL
ALCOHOL SYNDROME. THIS HAS A RANGE WHERE YOU CAN HAVE MINOR EFFECTS TO
VERY SIGNIFICANT EFFECTS OF THIS. SO ALCOHOL CHANGES THE DEVELOPMENTAL TRAJECTORY
OF THE FETUS, ASSUMING ALCOHOL IS GOING TO IMPACT THAT DEVELOPMENT
OF THAT INDIVIDUAL. TOLERANCE. SO WHAT WE SEE IS THAT IF YOU TAKE A DRUG IN THIS CLASS ONE TIME, YOU’LL HAVE A CERTAIN
EFFECT. BUT IF YOU CONTINUE TO TAKE THAT EFFECT OR CONSUME THAT
DRUG OVER A LONG-TERM, YOU’RE GOING TO HAVE TO CONSUME MORE OF THAT
DRUG TO GET THAT SAME ORIGINAL EFFECT. SO MAYBE YOU’VE HAD THIS EXPERIENCE WHERE
THE FIRST TIME THAT YOU DRANK ALCOHOL YOU FELT THAT
EFFECT VERY QUICKLY. AND THEN AFTER A COUPLE OF TIMES DRINKING OR SO,
YOU SEE THAT IT TOOK MORE ALCOHOL TO GET THE SAME EFFECT. SO YOU’VE BUILT THAT TOLERANCE. WHAT’S INTERESTING TO NOTE ABOUT THIS WITHIN
THIS GROUP IS THAT YOU CAN GET CROSS TOLERANCE. SO THAT, FOR EXAMPLE, YOU DRINK A LOT OF ALCOHOL AND YOU BUILD YOUR
TOLERANCE, THAT’S GOING TO HAVE ITS EFFECT HERE AND CHANGE THE FUNCTIONING
OF THE GABAergic SYSTEM AND IT’S FIRING SO THAT NOW BENZODIAZEPINES
OR THESE OTHER AGENTS MAY BE LESS EFFECTIVE. SO YOU CAN SEE CROSS TOLERANCE FROM DRUGS
IN THIS CONTINGENT OF THE ANTI-ANXIETY AGENTS AS WELL
AS THE SEDATIVE HYPNOTICS. ANOTHER ISSUE THAT WE’VE TALKED ABOUT IS POTENTIAL COMA AND DEATH BY COMBINING THESE DRUGS TOGETHER. AND BOTH THESE DRUG’S AGENTS HAVE THE POTENTIAL FOR BEING
A HIGHLY ABUSED POTENTIAL. SO THAT’S ANOTHER COMPLICATION ASSOCIATED
WITH THIS CLASS OF DRUGS. SO IN TERMS OF OUR NEXT CLASS OF DRUGS, WE’LL
TALK A LITTLE BIT ABOUT ANTIPSYCHOTIC AGENTS OR DRUGS
THAT ARE FUNCTIONING — WE’LL TALK ABOUT THEIR MECHANISMS OF ACTION. THEY WERE REALLY DEVELOPED VERY EARLY ON. WE FOUND THAT THESE DRUGS WERE VERY EFFECTIVE IN TREATING INDIVIDUALS THAT HAD SCHIZOPHRENIA. AND WHAT WE FIND IS THAT THERE IS THIS GRADUAL FROM 1946 TO 1955
GRADUAL INCREASE IN THE NUMBER OF PATIENTS THAT WERE BEING ADMITTED
INTO MENTAL INSTITUTIONS. AND THE DEVELOPMENT OF THESE DRUGS WE SEE
THERE IS A DRAMATIC DECLINE IN THEIR RESIDENCY HERE UNTIL WE GET OUT TO
1970 AND ALL THE WAY THROUGH 2000 THAT THERE’S A DRAMATIC DECREASE. AND THAT IS LARGELY DUE TO THE EFFECTIVENESS OF THESE DRUGS TO INFLUENCE
NEUROTRANSMISSION OR AT LEAST ATTENUATE NEUROTRANSMISSION AND THE
GOVERNMENT SYSTEM TO TREAT SCHIZOPHRENIA. NOW, WHAT WE’VE TALKED ABOUT AND JUST PREVIOUSLY
IS THAT THEY FUNCTION AT THE DOPAMINE RECEPTOR. THESE ANTIPSYCHOTIC AGENTS WORK TO PREVENT NEUROTRANSMISSION BY
BLOCKING THAT DOPAMINE RECEPTOR. ONE OF THE SIGNIFICANT COMPLICATIONS WE SEE
WITH THESE DRUGS IS THAT THESE PEOPLE WILL DEVELOP PARKINSON’S
TYPE OF DISORDERS OR DISKINESIAS. THAT MEANS THERE’S A DISORGANIZATION OF MOVEMENT
THAT WE SEE WITH THEM. WE ALSO SEE, ON THE OTHER HAND, PEOPLE THAT
TAKE THESE KINDS OF DOPAMINE AGONISTS, START TO SHOW
SOME SYMPTOMS ASSOCIATED WITH SCHIZOPHRENIA, SUCH AS SOME HALLUCINATIONS. SO WHAT WE SEE WITH THESE MECHANISMS OF ACTION — JUST A SECOND. LET ME — SORRY ABOUT THAT. SO WE’RE BACK HERE TALKING ABOUT THESE ANTIPSYCHOTIC AGENTS AND TALKING ABOUT THEIR MECHANISM OF
ACTION AND THAT THEY INFLUENCE FUNCTION AT THE DOPAMINE RECEPTOR. THEY BASICALLY ARE DOPAMINE ANTAGONISTS. AND ONE OF THE THINGS IS BECAUSE YOU’RE BLOCKING DOPAMINE AT THIS RECEPTOR, YOU’RE GOING TO
SEE SOME OF THESE SYMPTOMS YOU SEE ASSOCIATED WITH PARKINSON’S DISEASE. BECAUSE, REMEMBER, PARKINSON’S DISEASE YOU SEE PROBLEMS WITH
NEUROTRANSMISSION. THERE ISN’T ENOUGH DOPAMINE. SO BY BLOCKING THIS, PEOPLE WITH SCHIZOPHRENIA WILL OFTEN START TO SHOW SOME OF THOSE MOVEMENT
PROBLEMS. PROBLEMS INITIATING MOVEMENT. PROBLEMS AND TREMORS. THOSE KINDS OF COMPONENTS. WITH THAT, WE SEE IF WE RAMP UP OR WE HAVE
TOO MUCH NEUROTRANSMISSION WITHIN THE DOPAMINE SYSTEM
WHEN WE START TO GIVE HIGH DOSES OF AMPHETAMINE OR COCAINE, WE CAN SEE
THAT THEY START TO EXHIBIT SOME OF THE PARANOIA AND OTHER SYMPTOMS ASSOCIATED
WITH SCHIZOPHRENIA. SOME OF THE HALLUCINATIONS. SO WE CAN SEE THAT THIS SYSTEM IS SOMEHOW RELATED TO DOPAMINE, BOTH SCHIZOPHRENIA OR
THESE KINDS OF DISORDERS. OUR NEXT CLASS OF DRUGS WE’LL TALK ABOUT ARE ANTIDEPRESSANTS. AND EXAMPLES OF THOSE ARE PROZAC, ZOLOFT AND
PAXIL OR FLUOXETINE. THESE ARE USED TO TREAT MAJOR DEPRESSION FOR
INDIVIDUALS. AND THEY’VE STARTED TO BE USED TO TREAT OBSESSIVE
COMPULSIVE DISORDER. SO MAJOR DEPRESSION WE SEE IS DEFINED AS PROLONGED
FEELINGS OF GUILT OR WORTHLESSNESS. FREQUENT THOUGHTS OF SUICIDE OR SUICIDAL THOUGHTS. AND IN TERMS OF PREVALENCE, WE SEE THAT AROUND
6% IN THE POPULATION HAVE THIS AT SOME POINT. OBSESSIVE COMPULSIVE DISORDER. THIS, AGAIN, IS A MAJOR PROBLEM WITH DAILY LIVING DUE TO OBSESSIVE
THOUGHTS, SUCH AS IDEAS YOU CAN’T GET OUT OF YOUR HEAD, WHETHER
YOU’RE CONCERNED ABOUT CERTAIN GERMS OR LEAVING CERTAIN THINGS ON
IN THE HOUSE, SUCH AS THE OVEN. OTHER KINDS OF THOUGHTS. THESE ARE IDEAS YOU CAN’T GET OUT OF YOUR HEAD. THOSE OBSESSIVE THOUGHTS THAT WILL THEN TRANSLATE
TO COMPULSIVE KINDS OF ACTIONS, SUCH AS IN ORDER
TO DEAL WITH THESE THOUGHTS ABOUT GERMS, YOU’LL START TO WASH
YOUR HANDS EXCESSIVELY OR THAT COMPULSION TO HAVE TO WASH YOUR HANDS
MUCH MORE EXCESSIVELY OR DO MORE RITUALISTIC BEHAVIORS TO KNOW SOMETHING
HAS HAPPENED. THOSE KIND OF CHECKING BEHAVIORS. SO BOTH OF THESE DISORDERS HAVE BEEN —
THESE ANTIDEPRESSANTS HAVE BEEN USED TO TREAT BOTH
OF THESE DISORDERS. SO WHAT ARE THEIR MECHANISMS OF ACTION OR HOW
DO THEY CHANGE OR INFLUENCE NEUROTRANSMISSION? WELL, WE SEE THAT THERE ARE TWO GENERATIONS
OF ANTIDEPRESSANTS. OUR EARLY, FIRST GENERATION ANTIDEPRESSANTS
WERE CALLED MAO INHIBITORS. MAO INHIBITORS INHIBIT OR PREVENT THE BREAKDOWN OF SEROTONIN WITHIN THE NEURON. SO WHAT WE SEE IS THAT THERE IS THIS MAO,
MONOAMINE OXIDASE, THAT NORMALLY BREAKS DOWN SEROTONIN. SO WHAT HAPPENS IS YOU CAN GIVE AN MAO INHIBITOR THAT PREVENTS THE
BREAK DOWN OF SEROTONIN RESULTS IN A NET INCREASE IN SEROTONIN AVAILABLE
TO BE BOUND — TO BE RELEASED. AND THAT IS AN AGONIST. SO MAO INHIBITORS WERE INITIALLY FOUND TO BE VERY EFFECTIVE IN TREATING SOME
OF THESE SYMPTOMS. ONE OF THE IMPORTANT COMPLICATIONS WITHIN
THE MAO INHIBITORS IS THAT THEY CAN BE ABSOLUTELY
LETHAL WHEN COMBINED WITH CERTAIN FOODS. SO A CERTAIN FOOD IF YOU EAT IT AND YOU’RE
ON THESE MAO INHIBITORS WILL KILL YOU. AND THAT IS SOMETHING
THAT YOU DON’T WANT TO GIVE TO SOMEONE THAT KNOWLEDGE WHEN THEY HAVE
THESE THOUGHTS OF SUICIDE. ESPECIALLY BECAUSE SOME OF THESE DRUGS, THESE ANTIDEPRESSANTS, OFTEN TAKE SEVERAL WEEKS,
TWO TO THREE WEEKS BEFORE THEY START TO BECOME EFFECTIVE. ON BOARD THEY’RE IMMEDIATELY HAVING AN IMPACT ON THE NEUROTRANSMISSION, BUT THEY
DON’T START WORKING UNTIL TWO TO THREE WEEKS AFTER YOU’VE BEEN TAKING THE
DRUGS. SO, AGAIN, MAO INHIBITORS FUNCTION TO INHIBIT MONOAMINE OXIDASE BREAKING DOWN SEROTONIN. SO IF YOU HAVE MORE SEROTONIN TO GO AROUND, YOU’RE ENHANCING THAT
SEROTONIN NEUROTRANSMISSION. SSRIs ARE THE NEXT GENERATION BUT WE DON’T
HAVE THOSE COMBINATIONS WITH CERTAIN FOOD ITEMS. BASICALLY SSRIs ARE SELECTIVE SEROTONIN REUPTAKE INHIBITORS. SO THEY’RE PREVENTING SEROTONIN FROM BEING REABSORBED PRESYNAPTICALLY. THAT MEANS NOW THERE’S MORE SEROTONIN AVAILABLE IN THE SYNAPSE, AND THEY
CAN BIND MORE AND HAVE ITS EFFECT POSTSYNAPTICALLY. SO THOSE ARE ANOTHER WAY THAT WE CAN ENHANCE NEUROTRANSMISSION WITHIN THE SEROTONERGIC
SYSTEM. SO ONE OF THE INTERESTING THINGS ABOUT THESE
DRUGS THAT ARE USED TO TREAT ANTIDEPRESSANTS SPECIFICALLY,
MAO INHIBITORS AND REALLY SSRIs IS THAT THEY TAKE TWO TO THREE
WEEKS TO HAVE THEIR EFFECT. BUT THEY ARE IMMEDIATELY ENHANCING NEUROTRANSMISSION. AND IT’S LED PEOPLE TO TRY TO FIND, WELL, WHAT’S GOING
ON THERE. SO ENHANCING SEROTONIN IMMEDIATELY, WHY ARE THE RULES IMMEDIATELY
GETTING BETTER. AND ONE OF THE THINGS THAT’S RECENTLY BEEN
OBSERVED IS THAT THESE SSRIs ARE ASSOCIATED WITH THE INCREASE
IN NEW NEURONS, SPECIFICALLY IN THE HIPPOCAMPUS. SO SOME PEOPLE HAVE BECOME REALLY INTERESTED IN UNDERSTANDING THE INCREASE,
AND THOSE NEW NEURONS TAKES PLACE WITHIN ABOUT TWO WEEKS, WONDERING WHETHER
OR NOT MAYBE THOSE NEW NEURONS ARE PART OF THE MECHANISM OF ACTION
FOR THESE SSRIs. BUT MORE WORK IS GOING ON. THIS IS VERY EARLY DISCOVERING THIS AND TRYING TO SEE WHY BEHAVIOR
SYMPTOMS IMPROVE ARE SO LAGGED FROM THE MECHANISM OF ACTION AND NEUROTRANSMISSION
IS SO QUICK AND THEY NEED THAT LINK OF NEW NEURONS AS
BEING AN IMPORTANT ROLE. SO OUR LAST GROUP OF DRUGS THAT WE’LL TALK
ABOUT NARCOTIC ANALGESICS ARE MORPHINE AND HEROIN,
AND THEY’RE USED TO INDUCE SLEEP OR REDUCE PAIN. REALLY MORPHINE IS ONE OF THE MOST EFFECTIVE PAIN RELIEVERS THAT A PHYSICIAN HAS. IT IS JUST MORE EFFECTIVE IN REDUCING PAIN. AND IT’S ACTING THERE IN THOSE ENDOGENOUS
OPIOID RECEPTOR SITES THAT WE TALKED ABOUT IN THE
PERIAQUEDUCTAL GRAY MATTER. IT’S ACTING IN OTHER MATTERS. BUT IT’S FUNCTIONING TO SHUT DOWN THOSE PAIN SIGNALS. SO IT’S A VERY EFFECTIVE PAIN RELIEVER. HEROIN IS BETTER ABLE — IT’S LIKE MORPHINE
THAT IT’S ABLE TO REDUCE PAIN BUT IT’S MORE SOLUBLE
IN FATS. SO HEROIN IS ABLE TO CROSS THROUGH THOSE PHOSPHOLIPID BILAYERS
AND GET THROUGH THE BLOOD-BRAIN BARRIER QUICKER THAN MORPHINE
IS. SO WHEN YOU THINK ABOUT MECHANISMS OR THOSE ROUTES OF ADMINISTRATION,
HEROIN IS GOING TO ZOOM THROUGH THERE, WHEREAS MORPHINE IS GOING TO
TAKE A LITTLE MORE TIME. IT CAN STILL GET THROUGH, BUT HEROIN IS GOING
TO BE MORE SOLUBLE AND GET TO THE BRAIN QUICKER. THE SITE OF ACTION, AGAIN, IS AT THOSE ENDOGENOUS OPIOID RECEPTORS WE WERE TALKING ABOUT. CERTAIN KINDS OF COMPLICATIONS IS THAT AS YOU INCREASE THAT DOSE OF THESE
NARCOTIC ANALGESICS AS YOU’RE GOING TO SUPPRESS RESPIRATION. SO INCREASING THOSE DOSES, YOU START TO TURN OFF AND SUPPRESS RESPIRATION. THEY ALSO HAVE A HIGH ABUSE POTENTIAL. SO THEY’RE VERY, VERY, VERY HIGHLY ABUSED DRUGS. SO, FOR EXAMPLE, THERE’S A RECENT CHANGE IN — OVER GENERATIONS THERE’S
A CHANGE IN DRUGS THAT ARE PREFERRED FROM STIMULANTS, LIKE AMPHETAMINES,
TO NARCOTICS, SUCH AS MORPHINE OR HEROIN. AND NOW OXYCONTIN IS ALSO A PART OF THAT GROUP THAT’S HIGHLY ABUSED POTENTIAL. SO LET’S TURN NOW TO HOW EXPERIENCE WITH THE
DRUG CAN CHANGE ITS EFFECTIVENESS. AND WE TALKED A LITTLE BIT ABOUT THIS IDEA. DRUGS CAN LOSE THEIR EFFECTIVENESS OVER TIME. AND THAT’S REFERRED TO AS TOLERANCE OR A DRUG DECREASES ITS EFFECTIVENESS
OVER MANY ADMINISTRATIONS. AND YOUR BOOK TALKS ABOUT, AND I LIKE TO BRING
IT UP HERE AND HIGHLIGHT IT FOR A COUPLE OF REASONS. FIRST BASIC BRAIN BEHAVIOR THAT DRUGS CAN CHANGE THEIR EFFECTIVENESS
AND THEY HAVE GOOD EVIDENCE OF THAT. YOUR BOOK TALKS ABOUT A STUDY WITH PEOPLE
EXPOSED TO ALCOHOL. AND THESE WERE PRISONERS THAT WERE ABLE TO
ELECT TO PARTICIPATE IN THIS STUDY WHERE THEY WERE
GIVEN FREE ACCESS TO AS MUCH ALCOHOL AS THEY WANTED. AND THEY WERE THEN MONITORED FOR THEIR BLOOD ALCOHOL CONTENT AS WELL AS MONITORED FOR THE
BEHAVIORAL LEVEL OF INTOXICATION THAT THEY HAD. AND SO FOR THESE INDIVIDUALS, AND I FORGET
THE EXACT PAGE THIS GRAPH COMES FROM, BUT THE STUDY
WAS DONE BY ISABELLE AND OTHERS IN 1955. AND WHAT THEY DID WAS THEY LOOKED AT THEIR
— HOW MUCH ALCOHOL THEY WERE CONSUMING ACROSS 20 DAYS. SO THEY WERE GIVEN AS MUCH ALCOHOL AS THEY WANT A DAY FOR 13 WEEKS. AND THEN THEY MONITORED HOW MUCH ALCOHOL THEY CONSUMED. AND THEY LOOKED AT THE BLOOD ALCOHOL LEVEL ACROSS THOSE DAYS. AND WHAT YOU NOTICE IS THAT ALTHOUGH THE ALCOHOL
LEVEL INTAKE INCREASED ACROSS DAYS, THE BLOOD ALCOHOL
CONTENT SHOWED A VERY DIFFERENT FUNCTION. HERE IT INCREASED WITH THE INCREASING AMOUNT
OF ALCOHOL. BUT AT SOME POINT AROUND TEN DAYS HERE, WE
SEE IT STARTS TO LEVEL OFF. AND THEN THE AMOUNT OF ALCOHOL
IN THE BLOOD ACTUALLY DECREASES. AND WE SEE THAT THERE’S A CHANGE WHERE THERE’S
ACTUALLY A REDUCTION. SO THE BODY IS CHANGING IN RESPONSE TO THAT
ALCOHOL LEVEL. AND WE SEE THAT THAT AVERAGE DEGREE OF INTOXICATION
ALSO CHANGED. AND WE SEE THAT THAT DECREASED WITH THAT. AND IT FOLLOWS A SLIGHTLY DIFFERENT TIME FRAME
HERE THAN WHAT WE SEE WITH THAT. SO THERE’S THE DISSOCIATION NOT ONLY FROM THE AMOUNT OF THE DRUG THAT’S BEING CONSUMED
BUT THE IMPACT ON THE BODY, THE LEVEL OF THE BLOOD IN THE ALCOHOL. AND THERE’S A CHANGE IN ITS EFFECT ON BEHAVIOR OR LEVEL OF INTOXICATION
THAT’S DISTINCT HERE. SO TOLERANCE APPEARS TO BE A VERY COMPLEX
PROCESS THAT INVOLVES THE BODY BUT ALSO THE BRAIN. AND SO I THINK THIS STUDY KIND OF DEMONSTRATES THAT. AND NOW OBVIOUSLY THERE’S A NUMBER OF POTENTIAL FACTORS THAT COULD CONTRIBUTE TO THIS. CHANGES IN THE LIVER. THE WAY THE LIVER CAN METABOLIZE THAT AND PREVENT
THAT BLOOD FROM STAYING — THE ALCOHOL OR THE DRUG STAYING IN THE CENTRAL
NERVOUS SYSTEM. THERE’S OBVIOUSLY CHANGES IN THE NEURONS THAT COULD
BE OCCURRING WHERE MAYBE THERE’S FORMATION OF ADDITIONAL RECEPTORS. OR YOU’RE DEPLETING CERTAIN NEUROTRANSMITTERS. THOSE KINDS OF THINGS CAN BE HAPPENING. BUT WHAT I WANT TO ARGUE, AND THIS IS WHERE
WE KIND OF CHANGE THE PACING A LITTLE BIT OF THE PRESENTATION
HERE, IS I WANT TO ARGUE THAT THERE’S EVIDENCE THAT LEARNING,
BASIC LEARNING PHENOMENON COULD ALSO BE INFLUENCING THE DEVELOPMENT
OF TOLERANCE. NOW, I DON’T MEAN TO HAVE YOU THINK THAT THAT
DOESN’T MEAN THERE AREN’T CHANGES IN THE BRAIN. WE SEE CLEARLY — OUR PREVIOUS CHAPTER ENDED WITH DISCUSSION OF HOW SYNAPSES
CHANGE TO SUPPORT MEMORY. AND LEARNING IS A FOUNDATION FOR MEMORY. SO THERE’S OBVIOUSLY GOT TO BE CHANGES OF THE CENTRAL NERVOUS SYSTEM THAT
ARE SUPPORTING THAT. SO I DON’T WANT YOU TO THINK THAT THIS LEARNING
SOMEHOW DOESN’T DEPEND ON CHANGES AT THE SYNAPSE. BUT WE WANT TO LOOK AT A CERTAIN TYPE OF LEARNING PROCESS. AND WE’LL TALK ABOUT THIS AS CLASSICAL CONDITIONING. AND THAT CLASSICAL CONDITIONING MAY BE CONTRIBUTING
TO SOME OF THIS TOLERANCE THAT WE’RE SEEING HERE. WE WON’T USE ALCOHOL IN OUR EXAMPLE, BUT THERE MAY BE SOMETHING THAT’S GOING ON
WHERE THE BODY IS LEARNING TO PREPARE FOR THAT DRUG ADMINISTRATION. AND SO IT’S READY TO FEND THAT OFF. AND WE THINK THAT MAYBE SOME LEARNING
PROCESS IS CONTRIBUTING TO THAT, AND THAT’S CLASSICAL
CONDITIONING. NOW, EVERYBODY SHOULD BE FAMILIAR WITH CLASSICAL CONDITIONING FROM INTRO TO PSYCHOLOGY, OTHER
CLASSES THAT YOU MIGHT HAVE TAKEN. BUT WHAT I WANT TO DO HERE IS REVIEW THAT
A LITTLE BIT AND TALK ABOUT THOSE DIFFERENT FEATURES OF CLASSICAL
CONDITIONING. SO WITH CLASSICAL CONDITIONING, YOU REMEMBER
YOU HAVE AN UNCONDITIONED STIMULUS THAT’S FOOD. SO AN UNCONDITIONED STIMULUS WOULD BE FOOD. THAT MEANS UNDER ALL CONDITIONS, IT DOESN’T
MATTER, YOU GIVE A DOG FOOD AND IT’S GOING TO DROOL. SO IF YOU GIVE A DOG A LITTLE BIT OF FOOD, YOU’RE GOING TO SEE THAT IT DROOLS. THAT’S VERY CONSISTENT. IT’S A REFLEX THAT HAPPENS. THE FOOD IS GOING TO BE INGESTED. YOU NEED TO PREPARE THE BODY FOR THAT FOOD
THAT YOU’RE GOING TO INGEST, SO YOU’RE GOING TO INCREASE THE
SALIVA. SO THE DROOLING IS THE UNCONDITIONED RESPONSE. SO YOU PRESENT AN UNCONDITIONED STIMULUS, WHICH IS
FOOD, AND YOU GET THIS RESPONSE RIGHT AFTER PRESENTING THE FOOD OR
THE DROOLING OF THE DOG. SO THOSE ARE TWO COMPONENTS HERE FOR CLASSICAL
CONDITIONING. HOPEFULLY THIS IS FAMILIAR FOR FOLKS. NOW, WHAT HAPPENS IF YOU START PAIRING A SOUND
WITH THE FOOD. SO IF WE GIVE, FOR EXAMPLE, SOME SOUND. SO EVERY TIME THAT WE GO TO GIVE THE FOOD, WE RUN A CAN OPENER
OR SOMETHING LIKE THAT. OR WE GO INTO A DRAWER TO TAKE OUT SOME KIND
OF OBJECT TO OPEN UP, SUCH AS A CAN OPENER. SO THESE ARE ALL SOUNDS THAT ARE ACTUALLY
PAIRED WITH THE DELIVERY OF FOOD. THAT TONE OR THAT ENVIRONMENTAL STIMULUS IS REFERRED TO AS A CONDITIONED STIMULUS OR CS. REMEMBER THE FOOD IS THE US. IF WE REPEATEDLY GIVE THAT SOUND, WHETHER IT’S THE CAN OPENER, ELECTRONIC
CAN OPENER, WE’RE GOING INTO A SILVER WEAR DRAW TO TAKE OUT
A METAL CAN OPENER, THOSE ARE SOUNDS THAT START TO ALWAYS PREDICT THAT YOU’RE
GOING TO GET FOOD. AND SO WHAT WE SEE IS MULTIPLE PAIRING OF
THE CS AND US. AND BECAUSE YOU’RE GIVING THE US, YOU ALWAYS
GET THE UNCONDITIONED RESPONSE OR THE UR. WHAT’S GOING TO HAPPEN IS IF YOU PRESENT THE
CS ONE TIME BY ITSELF, SO YOU GO INTO THE KITCHEN
AND YOU TAKE AND GET THE ELECTRIC CAN OPENER GOING, YOUR DOG IS GOING
TO COME OVER AND START TO DROOL OR THINK IT’S GOING TO GET FOOD. SO THERE ARE GREAT EXAMPLES OF THIS ON THE
INTERNET OF CLASSICAL CONDITIONING. YOU MIGHT WANT TO GO ON TO YOUTUBE AND DO
A SEARCH, WHICH WE COULD DO RIGHT NOW. I THINK I’LL TRY THIS. IT’S ALWAYS A LITTLE SCARY WHEN YOU GO TO YOUTUBE
TO SEE WHAT IS GOING TO COME UP WHEN I PUT THIS. BUT LET’S SEE WHAT HAPPENS. AND I’LL PUT YOUTUBE IN HERE. AND PUT CLASSICAL
CONDITIONING IN. SORRY. I JUST CLOSED OUT. WHAT I’LL DO IS I’LL PAUSE THIS. ALL RIGHT. WE’RE BACK. I FOUND THE CLIP I WAS LOOKING FOR. LET’S SEE IF IT WORKS HERE. AND IT’S A LITTLE BIT LOW. I CAN’T HEAR IT. [ YOUTUBE CLASSICAL CONDITIONING THE OFFICE,
PAVLOV THEORY]>>PROFESSOR: I ALWAYS LAUGH WHEN I SEE THAT. SO, AGAIN, YOU MIGHT WANT TO SEARCH YOUTUBE. YOU MAY WANT TO TRY TO SEARCH YOUTUBE FOR CLASSICAL CONDITIONING, THE OFFICE,
TO GET A BETTER AUDIO VERSION OF THAT THAN WHAT WE HAVE HERE. BUT IT KIND OF ILLUSTRATES THAT — IT ILLUSTRATES THAT EFFECT OF CLASSICAL
CONDITIONING WHERE YOU’RE PAIRING CS WITH THE US. IN THAT SITUATION THE CS, THE CONDITIONED STIMULUS WAS THE NOISE ON JIM’S
COMPUTER. AND THE US WAS THAT ALTOID OR THAT BREATH MINT. AND WHAT YOU SEE IS THAT HE CONTINUED TO PAIR THEM SO HE GAVE ON ONE TRIAL THE CS
BY ITSELF. THE TONE. AND YOU SAW THAT DWIGHT HAD THAT RESPONSE OF MOUTH
BEING DRY AND ASKING FOR ANOTHER ALTOID. SO THE QUESTION IS CAN WE APPLY THIS, CAN
THIS IDEA OF CLASSICAL CONDITIONING AND LEARNING ABOUT
EVENTS, STIMULI IN OUR ENVIRONMENT, TO EXPLAIN SOME OF THE PHENOMENON
WE SEE WITH TOLERANCE, AND SPECIFICALLY DRUG TOLERANCE. AND SO TO DO THAT, HERE IS WHAT THE STIMULI WOULD BE. SO THE UNCONDITIONED STIMULUS WOULD BE MORPHINE. THE UNCONDITIONED STIMULUS WOULD BE MORPHINE. MUCH LIKE FOOD IS AN UNCONDITIONED STIMULUS. NOW, THE UNCONDITIONED RESPONSE THAT MORPHINE
ELICITS IS ANALGESIA OR REDUCED PAIN SENSITIVITY. SO YOU’RE NOT GOING TO BE AS SENSITIVE TO PAIN AFTER RECEIVING MORPHINE. AND JUST LIKE WITH REFUSAL TO GIVE FOOD, YOU WOULD SEE DROOLING. YOU GIVE MORPHINE, YOU SEE ANALGESIA. THE UNCONDITIONED STIMULUS IS MORPHINE. THE UNCONDITIONED RESPONSE IS ANALGESIA. NOW, WHAT WOULD BE A POSSIBLE CONDITIONED
STIMULUS? DWIGHT USED THAT TONE. WE USED A TONE WITH OUR DOGS TALKING ABOUT THAT. WE COULD USE ENVIRONMENTAL CUES. CUES IN THE ENVIRONMENT, SUCH AS WHAT OUR BEDROOM LOOKS LIKE OR WHAT A BATHROOM
LOOKS LIKE OR A CLUB. THESE ARE ALL POSSIBLE ENVIRONMENTAL CUES
THAT ARE AVAILABLE TO USE WHEN A DRUG IS BEING ADMINISTERED. SO WE CAN PAIR — IF WE WERE TO GIVE MORPHINE IN THE EXACT SAME ENVIRONMENT
OVER SEVERAL DAYS, WE MIGHT SEE THE DEVELOPMENT OF A COMPENSATORY RESPONSE
THAT NEGATES OR PREVENTS MORPHINE’S EFFECT ON THE BODY. JUST LIKE WE SAW WITH ALCOHOL AND WHAT WE
ALSO SEE WITH MORPHINE TOLERANCE. SO MORPHINE TOLERANCE OCCURS OVER DAYS. THE FIRST TIME YOU TAKE MORPHINE, YOU SEE THAT
IT HAS A CERTAIN EFFECT IN REDUCING PAIN. BUT AS YOU CONTINUE TO TAKE MORPHINE OVER
MULTIPLE DAYS, WHAT HAPPENS IS IT LOSES ITS EFFECTIVENESS
IN REDUCING PAIN. AND THIS IS PROBLEMATIC. BECAUSE WHAT HAPPENS IF YOU’RE IN PAIN OR YOU LIKE THE PLEASURABLE
EFFECTS OF MORPHINE, WHAT ARE YOU GOING TO DO IF YOU CONTINUE TO TAKE
THE DRUG AND YOU WANT TO GET THE SAME EFFECTS? WHAT WAS ONE OPTION THAT YOU COULD DO? YOU’LL INCREASE THE DOSE. AND SO AS THAT CONTINUES ON, YOU’RE GOING
TO CONTINUE TO INCREASE THE DOSE AND THAT CYCLE
CONTINUES. NOW, IF YOU CONTINUE TAKING THE DRUG IN THE
SAME ENVIRONMENT, THEN WHAT HAPPENS IF YOU GO INTO
A BRAND NEW ENVIRONMENT? YOU TAKE AWAY THOSE ENVIRONMENTAL CUES. IN THAT SITUATION, YOU’LL BE GIVING THE SAME DOSE OF MORPHINE. IT’S MUCH HIGHER THAN YOU WERE EVER ABLE TO TOLERATE THE FIRST TIME. BUT NOW YOU DON’T HAVE THE BODY BEING PREPARED FOR THAT. AND WHAT WE SEE IS THAT YOU’LL TEND TO OVERDOSE. SO THIS IS EXACTLY WHAT SHEP SIEGEL, A CANADIAN NEUROSCIENCE RESEARCHER WAS INTERESTED IN,
AND HE KIND OF SUGGESTED THIS IDEA THAT CLASSICAL CONDITIONING MAY
BE IMPORTANT FOR THE DEVELOPMENT OF TOLERANCE TO CERTAIN DRUGS
AND IMPORTANT FOR DIFFERENT ASPECTS OF DRUG TOLERANCE, SUCH AS OVERDOSING
AND HEROIN ADDICTS. HE GOT THIS BECAUSE HE DID SOME VITALOGS,
KIND OF A NEAT INSIGHT INTO SOME OF THE WAYS THAT WE
ACTUALLY DO SCIENCE. SHEP SIEGEL WAS INTERESTED IN DRUG ADDICTION, AND
HE GOT SOME REPORTS THAT OFTEN TIMES PEOPLE OVERDOSING FROM HEROIN
WOULD BE LEFT THERE DISCOVERED ON THE SCENE WHERE THEY HAD OVERDOSED
AND THEY WOULD HAVE ONLY INJECTED A FRACTION OF WHAT THEY NORMALLY
INJECT. AND THEY WOULD ACTUALLY STILL HAVE THE SYRINGE IN THEIR ARM
WITH PART OF THE HEROIN STILL IN THE SYRINGE. AND AFTER INTERVIEWING SOME OF THE PEOPLE
THEY WERE WITH, THEY SAID, YES, THIS PERSON HAD
ALWAYS INJECTED THIS AMOUNT OF HEROIN AND THERE HADN’T BEEN ANY PROBLEMS. SO IN THIS SITUATION IN THE INTERVIEWS HE
FOUND THAT SOME OF THESE PEOPLE WERE INJECTING FOR THE
FIRST TIME IN A PLACE THEY HAD NEVER INJECTED BEFORE. IT WAS A BRAND NEW PLACE. BUT BECAUSE THEY WERE USED TO INJECTING THIS CERTAIN AMOUNT,
THEY HAD DEVELOPED TOLERANCE AND THEY HAD UPPED THAT DOSE. NOW THEIR BODY WASN’T PREPARED. THEY DIDN’T HAVE THE CONDITIONED STIMULI AVAILABLE
TO — THE CONDITIONED STIMULI AVAILABLE TO PREPARE THE
BODY FOR THIS MUCH HIGHER DOSE OF MORPHINE OR HEROIN THAT THEY WERE
TAKING. SO HE SAW THIS OCCURRING IN INDIVIDUALS, PEOPLE,
BUT HE WANTED TO STUDY IT. HE WANTED TO INVESTIGATE THIS AND DEMONSTRATE THAT CLASSICAL CONDITIONING MIGHT BE AN IMPORTANT
FACTOR HERE. AND SO HE WANTED TO DEVELOP A PROCEDURE TO DO THIS
WITH RATS. SO WHAT HE DEVELOPED WAS A WAY TO ASSESS PAIN IN RATS
THAT WOULDN’T CAUSE ANY KIND OF — IT WOULDN’T CAUSE ANY PERMANENT DAMAGE. IT WOULD JUST BE UNCOMFORTABLE. HE WOULD THEN GIVE THEM MORPHINE TO SEE WHAT
IT WOULD DO TO THAT RESPONSE. AND THEN SEE WHAT HAPPENS IF HE CHANGED HIS CONTEXT. HOW WOULD THEY DO? HOW WOULD THEY RESPOND? AND SO WE’RE GOING TO TALK ABOUT A SERIES
OF STUDIES THAT HE DID, EXPERIMENTS. AND WE’RE GOING TO GO SLOWLY THROUGH THIS
SO THAT YOU GET A GOOD IDEA OF WHAT — HOW THE
EXPERIMENT WAS SET UP, WHAT THE RESULTS ARE AND WHAT THEY SUPPORTED WITH
THE IDEA THAT I’M TRYING TO MAKE AN ARGUMENT, I’M TRYING TO CONVINCE
YOU THAT CLASSICAL CONDITIONING ALSO PLAYS A ROLE IN DEVELOPMENT
OF DRUG TOLERANCE AND MORPHINE TOLERANCE. SO THIS STUDY HE HAD SEVERAL GROUPS. HERE WHAT WE SEE ARE — IN THIS STUDY HE HAD A COUPLE OF GROUPS. AND IT WAS SET UP SO THAT THESE ANIMALS RECEIVED MORPHINE AND WERE
ASSESSED FOR THEIR PAIN TOLERANCE ON DAY ONE, DAY TWO, DAY THREE AND
DAY FOUR. AND BASICALLY WHAT YOU CAN DO IS SET UP A ROOM THAT IS MAYBE
DARK AND IT’S QUIET BUT MAYBE IT SMELLS LIKE VANILLA OR LEMON. AND SO THAT CREATES A CONTEXT. AND SO YOU WOULD TAKE THESE RATS INTO THAT
ROOM, INJECT THEM WITH MORPHINE, AND THEN PUT THEM
ON THE HOT PLATE AND LOOK AT HOW DID THEY — HOW DID THEY RESPOND? NOW, A NORMAL RAT OR A RAT THAT ISN’T ON THE
MORPHINE, ONCE YOU PUT IT ON THIS PLATE, HOT PLATE THAT
HE USED, WHAT WOULD HAPPEN IS THE RAT WOULD PICK UP THEIR PAW
AND START LICKING IT IN TEN SECONDS INDICATING IT’S BECOMING UNCOMFORTABLE. BUT IF YOU GIVE THEM MORPHINE ON THAT — THE FIRST TIME THEY GO
ON THE HOT PLATE, WHAT YOU’LL SEE IS THEY’LL TAKE ABOUT 25 SECONDS
BEFORE THEY LICK THEIR PAWS. AS SOON AS THEY LICK THEIR PAWS, YOU TAKE
THEM OFF, TAKE THEM IN AND LET THEM RECOVER AND THEN TAKE THEM BACK
TO THEIR HOME CAGE. AND WHAT WE SEE HERE FOR THESE TWO GROUPS
IS THAT THE GROUP THAT DOESN’T RECEIVE SALINE OR DOESN’T
RECEIVE MORPHINE, THEY RECEIVE SALINE, THEY SHOWED A VERY CONSISTENT
TIME TO LICK THEIR PAWS ACROSS DAYS. SO THEY’RE NOT CHANGING. SO THE SALINE HOT PLATE GROUP, THESE DARK BLUE BARS HERE, SHOW THAT THEY
ARE REALLY NOT CHANGING THEIR LATENCY TO LICK THEIR PAWS. WHEREAS THE ANIMALS, THE RATS THAT RECEIVED
THE MORPHINE, WE SEE THAT ON DAY ONE THEY HAVE
MUCH LONGER LATENCY TO LICK THEIR PAWS DEMONSTRATING THAT MORPHINE IS
REDUCING THEIR SENSITIVITY TO PAIN. SO THEY’RE ABLE TO SEE A BEHAVIORAL EFFECT
OF MORPHINE IN TERMS OF REDUCING THEIR SENSITIVITY TO PAIN. BUT WHAT WE ALSO NOTICE IS FROM DAY ONE TO
DAY TWO, MORPHINE ISN’T AS EFFECTIVE AS IT WAS BEFORE. SO HERE FROM DAY ONE TO DAY TWO, WE SEE THAT THERE’S A REDUCTION IN
MORPHINE’S EFFECTIVENESS. THAT DEFINITION OF TOLERANCE. AND BY DAY THREE, IT’S EVEN LESS EFFECTIVE. NOW, DAY FOUR WHAT WE’RE GOING TO DO IS THESE
TWO GROUPS WILL BE TESTED AGAIN WHERE WE’LL SEE WHAT
HAPPENS WHEN WE INJECT THEM IN THE HOT PLATE ROOM WITH MORPHINE OR SALINE. NOW, WE HAVE A THIRD GROUP I HAVEN’T TOLD
YOU ABOUT YET. THIS IS A GROUP MORPHINE CAGE. AND WE COULDN’T ASSESS THEIR SENSITIVITY TO PAIN ON MORPHINE BECAUSE WE
WANTED TO TEST THEM AND HAVE THEM DEVELOP TOLERANCE IN AN ENTIRELY DIFFERENT
CONTEXT. LIKE THOSE PEOPLE THAT HAD BEEN INJECTING MAYBE IN THEIR
BEDROOM AND UPPING THAT DOSE MULTIPLE TIMES AND THEN ONE DAY THEY
GO OUT PARTYING WITH THEIR FRIENDS AND THEY INJECT IN A BATHROOM AT A
BUSINESS OR A BAR. AND SO WE WANTED TO BE ABLE TO HAVE THEM DEVELOP TOLERANCE AND THEN CHANGE THE CONTEXT ON DAY
FOUR FOR THEM. THEY RECEIVED THE IDENTICAL DOSE OF MORPHINE AS
THIS MORPHINE HOT GROUP PLATE DOES ON DAY ONE, DAY TWO AND DAY THREE. WE’RE JUST NOT ABLE TO ASSESS THEIR PAIN BECAUSE WE WANT THEM TO
BE RECEIVING THE DRUG IN A DIFFERENT CONTEXT FROM WHERE THEY’RE TRANSFERRED
TO, AND THEN WE CAN ADDRESS THEIR SENSITIVITY TO PAIN ON DAY FOUR. SO WE HAVE THREE GROUPS OF RATS. TWO GROUPS ARE BEING TESTED EVERY DAY IN THIS MORPHINE HOT PLATE
ROOM THAT’S DARK, THAT’S QUIET, MAYBE IT SMELLS LIKE LEMON ON DAY ONE,
DAY TWO AND DAY THREE. AND WE SEE THE MORPHINE GROUP THAT’S RECEIVING
THE EXACT SAME DOSE ON DAY ONE, DAY TWO, DAY THREE IS SHOWING THAT
DEFINITION OF TOLERANCE. MORPHINE IS NOT AS EFFECTIVE IN REDUCING PAIN. THE SALINE GROUP IS SHOWING A VERY STABLE
LATENCY TO LICK THEIR PAWS ACROSS DAYS. THEY’RE GETTING SALINE INJECTED IN THAT HOT PLATE ROOM. AND THEN WE HAVE ANOTHER GROUP OF ANIMALS
THAT ON DAY ONE GETS THE SAME DOSE AS THIS GROUP DID,
BUT THEY JUST STAY IN THEIR HOME CAGE. ON DAY TWO THEY GET THE SAME DOSE OF THE DRUG
AS DAY TWO AS THE MORPHINE HOT PLATE GROUP AND ON DAY THREE
THEY GET THE SAME DOSE. BUT WE’RE NOT ASSESSING THEIR PAIN UNTIL DAY
THREE WHEN THEY GO INTO A BRAND NEW CONTEXT. SO THAT CONTEXT IS NEW. THEY’VE NEVER BEEN THERE. SO THAT MEANS BASED ON OUR CLASSICAL CONDITIONING MODEL, THEY ARE GETTING A CONDITIONED STIMULUS
— I MEAN, THEY’RE GETTING THE UNCONDITIONED STIMULUS, THE MORPHINE,
WITHOUT THE CONDITIONED STIMULUS. THE CONTEXT. ALL RIGHT. SO THIS GROUP MORPHINE CAGE IS GETTING THE UNCONDITIONED STIMULUS,
THE MORPHINE, WITHOUT THE CONDITIONED STIMULUS, THE CONTEXT. AND SO WHAT WE PREDICT IS THAT THEY WOULD
SHOW THAT MORPHINE NOW IS EFFECTIVE. AND THAT’S EXACTLY WHAT SHEP SIEGEL OBSERVED IS THAT OUR GROUP THAT RECEIVED ON
THAT DAY FOUR THAT HAD RECEIVED MORPHINE HERE ON DAY ONE, DAY TWO,
DAY THREE, DAY FOUR. NOW THEY’RE SHOWING THE EQUIVALENT AMOUNT OF LATENCY
AS WE SEE HERE FOR OUR SALINE TREATED GROUP. NOW, THE MORPHINE CAGE, THEY RECEIVED THE
SAME DOSE ON DAY FOUR AS THEY DID ON DAY ONE, DAY TWO,
DAY THREE, BUT THEY’RE JUST RECEIVING THE NEW CONTEXT. AND NOW THEY AREN’T AS SENSITIVE TO PAIN AS THESE TWO OTHER GROUPS. SO MORPHINE NOW IS EFFECTIVE FOR THIS GROUP. AND THE ONLY DIFFERENCE BETWEEN THIS MORPHINE
CAGE AND THE MORPHINE HOT GROUP IS THAT THIS GROUP IS RECEIVING THIS
MORPHINE IN THE NEW CONTEXT DEMONSTRATING EVIDENCE THAT WHERE YOU RECEIVE
THE DRUG IS REALLY IMPORTANT. AND IF YOU CHANGE THAT LOCATION OR THE ENVIRONMENT
AND YOU STILL HAVE THE HIGH DOSE FOR THOSE PEOPLE
THAT HAVE BEEN UPPING THAT DOSE OF MORPHINE AND YOU GO INTO A NEW PLACE
AND YOU INJECT WITH THAT SAME HIGH DOSE, YOU CAN OVERDOSE VERY EASILY. SO THIS WAS A NICE TRANSLATION FROM WHAT SHEP
SIEGEL OBSERVED ON HIS RIDE ALONG WITH THESE CALLS
FOR PEOPLE THAT HAD OVERDOSED FROM HEROIN TO COME INTO THE LAB
AND SEE WHETHER ENVIRONMENT WAS REALLY AN IMPORTANT FACTOR. AND THIS WAS EVIDENCE, YES, WHERE YOU RECEIVE THOSE DRUGS HAS AN IMPACT AND THAT
HISTORY, IF YOU REPEATEDLY ADMINISTER A DRUG AND YOU SEE THE LEVEL OF
TOLERANCE AND YOU CHANGE THAT TO A NEW CONTEXT, THAT TOLERANCE GOES
AWAY. BASICALLY WHAT YOU’RE DOING IS YOU’RE GIVING
THE UNCONDITIONED STIMULUS, THE MORPHINE, PRODUCING
THE UNCONDITIONED RESPONSE, THE ANALGESIA, BUT YOU DON’T HAVE
THE CONDITIONED STIMULUS OR THE ENVIRONMENT THAT WILL PRODUCE THE COMPENSATORY
RESPONSE AND ELIMINATE OR REDUCE THE EFFECTS OF THAT DRUG
ON THE CENTRAL NERVOUS SYSTEM. SO THIS WAS ONE STUDY. ANOTHER STUDY WE WANTED TO LOOK AT WAS DESIGNED TO LOOK AT INDIVIDUALS
WHERE THEY JUST GIVE THEM A TIMEOUT AND YOU THEN — THE NEXT STUDY WAS
DESIGNED BASED ON AN OBSERVATION OF AN AD CAMPAIGN THAT HAPPENED
IN ENGLAND. WHAT THEY FOUND IS, YOU KNOW, THERE ARE DIFFERENT DRUG
CAMPAIGNS, AND THEY USE MEDIA TO PROMOTE AND DETECT THE NEW DRUGS. WELL, WHEN THEY INTRODUCED THIS NEW DRUG CAMPAIGN, WHAT THEY FOUND THE DRUG CAMPAIGN WAS BASICALLY
SHOWING A LOT OF PARAPHERNALIA, SOME OF THE STIMULI ASSOCIATED
WITH INJECTING AND ABUSING HEROIN. AND PEOPLE THAT HAD ABSTAINED FROM HEROIN
WHEN THEY SAW THESE SIGNS STARTED TO EXPERIENCE WITHDRAWAL
SYMPTOMS. SO YOU CAN IMAGINE WALKING THROUGH A SUBWAY
SEEING THE SIGN WHEN IT HAS ALL OF THE PARAPHERNALIA
ASSOCIATED WITH HEROIN ABUSE AND THIS PERSON HAD BEEN ABSTAINING, THEY
HADN’T BEEN ABUSING, THEY SEE THESE STIMULI, THE CONDITIONED STIMULI, AND
THEY DON’T HAVE THE HEROIN ON BOARD, THE UNCONDITIONED STIMULUS, AND
NOW YOU GET THE CONDITIONED RESPONSE WHICH IS COMPENSATORY AND THEY TRY
TO COUNTERACT THE EFFECTS AND GET THESE WITHDRAWAL SYMPTOMS. THEY START TO FEEL AS THOUGH YOU’RE AGITATED. YOU’RE IRRITATED. YOU DON’T FEEL GOOD. YOU START TO FEEL PAIN. AND YOU WANT TO REALLY GO BACK AND ABUSE OR
THINK OF THE DRUG AS A WAY TO ELIMINATE THESE SYMPTOMS. WELL, SHEP SIEGEL WANTED TO TAKE THAT PHENOMENA
THAT WAS OBSERVED IN THE WORLD AND BRING IT INTO
THE LAB. SO WHAT HE DID IS THE SAME KIND OF THING. WE HAVE A VERY SIMILAR GRAPH HERE. AND NOW THIS IS A COMPLETELY WITHIN SUBJECT GROUP. AND OUR GRAPH IS A LITTLE BIT DIFFERENT THAN WHAT YOU SEE HERE WHERE
WE’RE LOOKING AT CHANGE SCORES. SO BASICALLY ABOVE THE LINE AROUND 100 MEANS
THAT YOU’RE INCREASING THE LATENCY TO LICK YOUR PAW. AND
THEN BELOW THE LINE MEANS YOU’RE REDUCING YOUR LATENCY TO LICK PAW. AND SO WHAT WE SEE HERE WHEN WE ADMINISTER
MORPHINE OVER 4 DAYS, THERE’S THAT GRADUAL DECREASE
IN EFFECTIVE OF A MORPHINE — OF MORPHINE TO REDUCE SENSITIVITY TO PAIN. SO WE SEE THIS CHANGING ACROSS HERE OUR TOLERANCE. THEN WHAT WE DID OR WHAT SHEP SIEGEL DID WAS
HE GAVE A TWO WEEK TIMEOUT TO KIND OF WATCH THE RATS
GET THE MORPHINE OUT OF THEIR SYSTEM. AND THEN HE CAME BACK AND HE DID SOMETHING
THAT WAS VERY DIFFERENT. INSTEAD OF ADMINISTERING THE DRUG OR CHANGING
CONTEXT, HE TOOK THE RATS BACK INTO THE IDENTICAL CONTEXT
AND GAVE THEM SALINE. SO I GAVE THEM SALINE AGAIN. SO HE GAVE THEM SALINE AND INJECTED THEM FOR THEIR SENSITIVITY TO PAIN. SO AFTER THAT TWO WEEK TIMEOUT, HE GAVE THE
RATS THAT DEVELOPED TOLERANCE AN INJECTION OF SALINE. AND IF YOU THINK ABOUT, YOU’RE INJECTING SALINE, THAT SHOULD HAVE
NO EFFECT AT ALL. BUT CLASSICAL CONDITION IS IMPORTANT OR CONTRIBUTING
TO THE TOLERANCE THAT WE SEE IN DRUG ADDICTION. AND WE’RE GETTING THE CONDITIONED STIMULI WHICH PRODUCED THIS COMPENSATORY RESPONSE
IN THE ABSENCE OF THE US WHICH PRODUCES THE UR, WE MIGHT SEE SOMETHING
THAT’S IN OPPOSITION. AND THAT’S WHAT SHEP SIEGEL OBSERVED THAT
NOW WHEN YOU ADMINISTER SALINE, JUST SIMPLE SALINE, THESE ANIMALS
ARE LICKING THEIR PAWS MUCH FASTER THAN NORMAL. THEY WERE LICKING THEIR PAWS MUCH FASTER. SO THEY HAD THE CONDITIONED STIMULI THAT PRODUCED
THIS COMPENSATORY RESPONSE THAT WAS TRYING TO NEGATE
TRYING TO ELIMINATE THE EFFECTS OF THE DRUG. BUT THE DRUG ISN’T THERE. AND ESSENTIALLY SEEING THAT THESE ANIMALS ARE HYPERSENSITIVE TO PAIN. ONE OF THOSE FEATURES OF WITHDRAWAL SYMPTOM WITH PEOPLE THAT HAD
BEEN EXPOSED TO THAT AD CAMPAIGN SHOWED THAT THEY BECAME AGITATED
AND THEY FELT LIKE THEY WANTED TO USE THE DRUGS AGAIN TO REMOVE THOSE
OR ELIMINATE THOSE WITHDRAWAL SYMPTOMS. SO THIS IS FURTHER EVIDENCE THAT CLASSICAL CONDITIONING OR LEARNING CAN COME INTO INFLUENCE
THE DEVELOPMENT OF TOLERANCE TO DRUGS. SO OUR NEXT STUDY I’LL TALK ABOUT I’LL DESCRIBE
THE STUDY, THE THIRD EXPERIMENT HERE, AND I’LL
SEE WHETHER YOU CAN COME UP WITH WHAT YOU THINK WHETHER IT’S APPLIED OR
NOT. HERE WE HAVE TWO GROUPS OF ANIMALS, SAME KIND OF SETUP. NOW, AGAIN, I WANT TO POINT OUT THE Y AXIS IS SET UP SO THAT IF IT’S HIGHER
THAN THERE’S A DECREASE SENSITIVITY TO PAIN. IF IT’S LOWER, THAT BEING IF IT’S MORE REGULAR SENSITIVITY TO PAIN. WE HAVE TWO GROUPS OF ANIMALS INDICATED HERE
BY THE RED AND GREEN LINES. AND DURING TRIAL ONE, TRIAL TWO AND TRIAL THREE, WE SEE THAT THEY’RE SHOWING THEIR TYPICAL
REDUCED EFFECTIVENESS OF MORPHINE ACROSS TRIALS AND THEY’RE SHOWING
THAT THEY’RE NOW SENSITIVE TO PAIN LIKE NORMAL CONDITIONS HERE. AND THEN HOW THE GROUPS DIFFER, THE ONLY WAY
THESE TWO GROUPS DIFFER IS THAT DURING A TWO-WEEK TIMEOUT
PERIOD, ONE GROUP M-P-M, MORPHINE-PLACEBO-MORPHINE, RECEIVED
MULTIPLE PLACEBO INJECTIONS IN THE HOT PLATE ROOM. SO THEY RECEIVED AN INJECTION OF SALINE IN
THE HOT PLATE ROOM. THEY WEREN’T ASSESSED WITH THEIR PAIN. THEY JUST GOT THAT DRUG OR THE SALINE ADMINISTERED IN THE
HOT PLATE ROOM. SO WE’RE BASICALLY PRESENTING THE CS MULTIPLE TIMES
WITHOUT THE US. WE’RE GIVING THEM THE CONTEXT, THE PARAPHERNALIA,
EVERYTHING, MULTIPLE TIMES WITHOUT THE US OR THE DRUG ON BOARD. SO THAT’S WHAT WE’RE DOING. THE MORPHINE-REST-MORPHINE GROUP INSTEAD OF
BEING EXPOSED TO THE CONTEXT OR THE CS, THOSE ENVIRONMENTAL
CUES, IT JUST STAYED — THOSE RATS JUST STAYED IN THEIR
HOME CAGE FOR THE TWO WEEKS. BUT THE MORPHINE-PLACEBO-MORPHINE GROUPS WERE
GETTING DAILY INJECTIONS OF SALINE. NOW, GIVEN WHAT WE KNOW ABOUT DRUG EFFECTS
SO FAR, YOU REALLY WOULDN’T THINK THAT THERE SHOULD BE
AN EFFECT. AFTER THAT TWO WEEK PERIOD, BOTH GROUPS GET THE SAME EXACT
DOSE OF MORPHINE. THEY GET THE EXACT SAME DOSE OF MORPHINE. WE WOULD EXPECT THAT THEY SHOULD BOTH SHOW TOLERANCE. HOWEVER, IF LEARNING OR CLASSICAL CONDITIONING
IS COMING INTO PLAY AND WE’RE REPEATEDLY SHOWING
THE KRS WITHOUT THE US, THAT’S REFERRED TO AS EXTINCTION, RIGHT? THAT’S AN EXAMPLE WHERE WITH OUR DOG WE GIVE, SAY, THE CAN OPENER BUT NEVER
GIVEN FOOD, THE DOG IS EVENTUALLY GOING TO LEARN THAT THAT FOOD IS
NO LONGER COMING WITH THAT SOUND. AND WHAT WE WOULD EXPECT IF IT WAS CLASSICAL
CONDITIONING, WE HAVE EXTINCTION, WE SHOULD SEE A CHANGE IN
THE GROUP’S RESPONSIVENESS TO MORPHINE ON THAT DAY FOUR AFTER THAT TWO
WEEK — OR SESSION FOUR AFTER THAT TWO WEEKS OF PLACEBO INJECTIONS
FOR THIS GROUP AND JUST RESTING IN THE HOME CAGE FOR THIS GROUP. AND THAT’S EXACTLY WHAT WE FIND IS THAT GROUP
THAT RECEIVED THOSE PLACEBO INJECTIONS SHOW THAT
NOW THEY’RE NOT AS SENSITIVE TO PAIN OR MORPHINE IS MORE EFFECTIVE. SO THEY’RE SHOWING A DECREASED SENSITIVITY TO PAIN OR MORPHINE
IS NOW EFFECTIVE COMPARED TO THIS GROUP THAT STAYED IN THEIR CAGE, AND
NOW THEY’RE JUST AS SENSITIVE TO PAIN AS WE SEE DURING SESSION THREE. SO JUST TO REVIEW THESE EXPERIMENTS HERE,
WHAT WE’RE DOING IN OUR FIRST EXPERIMENT, JUST TO KIND
OF GO THROUGH THIS AGAIN TO GIVE YOU AN IDEA, IS HERE IN THIS EXPERIMENT
WE HAVE THREE GROUPS. WE’RE LOOKING AT THEIR SENSITIVITY TO PAIN. WHEN WE’RE UP HIGHER, THERE’S NO PAIN. DOWN HERE THERE IS PAIN. WE SEE WE GIVE MORPHINE. THEY’RE SHOWING A MUCH LONGER LATENCY TO LICK THEIR PAWS. THEY’RE NOT AS SENSITIVE TO PAIN. BUT THE EFFECTIVENESS OF MORPHINE DECREASES
ACROSS TRIALS, WHERE BY TRIAL FOUR THAT GROUP IS NOT AS SENSITIVE
TO PAIN. THE ARGUMENT IS THAT THEY ARE DEVELOPING A CONDITIONED ASSOCIATION
BETWEEN THE CONTEXT AND THAT DRUG. SO THAT WHEN THIS MORPHINE CAGE GROUP WHILE
THEY’RE NEVER ASSESSED FOR PAIN BUT WE SWITCHED THEM
TO NO CONTEXT AND THEY DON’T HAVE THE CS BUT THEY HAVE THE US, WE
SEE THAT THEY’RE SHOWING THAT MORPHINE IS VERY EFFECTIVE OR THEY’RE
SHOWING A DECREASED SENSITIVITY TO PAIN. FOR THE NEXT STUDY, WE LOOKED AT HERE IS A
DEVELOPMENT OF TOLERANCE. THIS IS A CHANGE SCORE HERE SHOWING THAT NOW
WE’RE LOOKING — TAKING MUCH LONGER TO LICK THEIR
PAWS TO NOW THEY’RE TAKING THE SAME TIME TO LICK THEIR PAWS AS THEY DID
PRIOR TO THE DRUG ADMINISTRATION. WE GIVE THEM A SALINE INJECTION AFTER A TWO-WEEK TIMEOUT PERIOD WHERE THEY NEVER ARE BACK IN
THAT ROOM, WE GIVE THEM SALINE, NOW THEY’RE LICKING THEIR PAWS MUCH
MORE QUICKLY THAN THEY WOULD NORMALLY SHOWING THAT MAYBE THEY’RE
MORE SENSITIVE TO STIMULI. IN OUR LAST STUDY WHAT WE DO IS ONE GROUP
GETS REPEATED EXPOSURE, THEY GET REPEATED EXPOSURES
TO THAT ROOM WHEN WE’RE TRYING TO EXTINGUISH THAT ASSOCIATION BETWEEN
THE CS AND THE US, THE CONTEXT AND THE DRUG. AND WHAT WE SEE HERE IS WHEN WE COME BACK
AND GIVE THEM MORPHINE ON THIS FOURTH SESSION,
THAT MORPHINE-PLACEBO-MORPHINE GROUP HERE THEY’RE
SHOWING US A DECREASE IN SENSITIVITY TO PAIN WHERE NOW MORPHINE IS
EFFECTIVE OR WE’VE WEAKENED THAT ASSOCIATION BETWEEN THE CS AND THE US. SO THE QUESTION IS HOW CAN THIS LAST STUDY
BE APPLIED TO HUMANS? HOW CAN WE APPLY THIS STUDY TO THE TREATMENT
OF DRUG ADDICTION IN HUMANS? WHAT YOU CAN DO IS PAUSE THE LECTURE AND THINK ABOUT IT FOR A LITTLE BIT. BECAUSE I’M GOING TO GIVE YOU THE ANSWER TO THIS QUESTION. SO SEE IF YOU CAN’T FIGURE OUT, TALK WITH
PEOPLE, SEE WHAT YOU COME UP WITH. BUT HERE IS THE ANSWER. THIS COULD BE APPLIED TO HUMANS BY LOOKING AT METHADONE TREATMENT. FIRST, METHADONE IS NICE BECAUSE IT’S A DIFFERENT ROUND OF ADMINISTRATION. PEOPLE ORALLY INGEST THIS. SO THEY AREN’T GOING TO HAVE THAT IMMEDIATE
PEAK IN BLOOD ALCOHOL OR BLOOD CONCENTRATION OF MORPHINE. AND IT WILL BE SUFFICIENT TO KEEP THE WITHDRAWAL SYMPTOMS AT BAY. BUT PEOPLE ON METHADONE GO BACK INTO THEIR
ENVIRONMENT AND THEY CAN EXTINGUISH SOME OF THOSE ASSOCIATIONS
BETWEEN THE DRUG AND THE ENVIRONMENT, THE CONTEXT. SO MAINTAINING THEM ON THAT METHADONE ALLOWS THEM TO NOT HAVE WITHDRAWAL SYMPTOMS. IT ALSO ALLOWS THEM TO BREAK SOME OF THOSE CONTEXT AND DRUG ASSOCIATIONS
AND THEN GRADUALLY OVER TIME TAPERING THEM ON A LOWER AND LOWER
DOSE OF METHADONE SO THAT THEN THEY CAN EVENTUALLY BE OFF. SO THEN WHEN THEY’RE COMPLETELY OFF, THEY
RETURN BACK TO THAT ENVIRONMENT, THEY SEE THOSE CUES,
THEY AREN’T GOING TO BE USING — BEGIN HAVING SOME OF THOSE WITHDRAWAL SYMPTOMS
BECAUSE YOU HAVE THE CS ENVIRONMENTAL CUES TURNING THE CR OR SOME
OF THOSE WITHDRAWAL SYMPTOMS. NOW, I HAVE TO TELL YOU THAT METHADONE TREATMENT
ISN’T 100% EFFECTIVE IN TREATING THIS, BUT IT DOES
HELP. IT IS A VIABLE OPTION FOR SOME FOLKS. AND UNDERSTANDING THAT CLASSICAL CONDITIONING DOES CONTRIBUTE PROCESSES, DOES CONTRIBUTE
TO THE TOLERANCE AND DEVELOPS THOSE DRUGS AND HELPS YOU DEVELOP
BETTER TREATMENTS. THIS WORK WAS DONE IN THE ’70s, 1975, AND
HAS BEEN FOLLOWED UP AND NOW PEOPLE ARE TRYING TO UNDERSTAND
WHAT PARTS OF THE BRAIN ARE CONTRIBUTING TO THIS LEARNING AND
DETERMINING THAT WE CAN DEVELOP MAYBE BETTER TREATMENTS TO ALLOW US
TO ELIMINATE THAT ASSOCIATION OR TRY TO CONTROL THAT PROCESS
MORE EFFECTIVELY. SO WE CONCLUDED OUR LAST CHAPTER FOR EXAM
THREE. THIS IS, AGAIN, CHAPTER 6 ON DRUGS AND BEHAVIOR. SO WHAT YOU’LL WANT TO DO IS FOR EACH CHAPTERS 4, 5 AND 6, YOU’LL WANT
TO GO THROUGH, REVIEW THE LECTURES, ATTEMPT THE LECTURE QUIZZES AND
ATTEMPT THE PRACTICE EXAMS. AND ONCE YOU FEEL LIKE YOU REALLY HAVE A GOOD
IDEA, MAKE SURE YOU’RE TAKING THE NOTES, REVIEW YOUR NOTES, RECOPY
YOUR NOTES AND TAKE NOTES FROM THE TEXTBOOK. YOU THEN WILL BE READY TO TAKE EXAM TWO. IT’S AVAILABLE. NOW, REMEMBER, EXAM TWO IS GOING TO BE COVERING CHAPTER 4, 5 AND 6. SO KEEP THAT IN MIND. AND I LOOK FORWARD TO TALKING TO YOU NEXT TIME. AND WE’LL GET TO TALK ABOUT DEVELOPMENT OF THE CENTRAL NERVOUS SYSTEM AND BEHAVIOR. GOOD LUCK ON EXAM TWO. TALK TO YOU SOON. BYE.

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