Psych 181: Dr. Anagnostaras

Lecture 4Lecture 4Behavioral PharmacologyBehavioral Pharmacology

Behavioral Pharmacology

Behavioral Pharmacology

The study of the relationship between The study of the relationship between the physiological actions of drugs and the physiological actions of drugs and their effects on behavior and their effects on behavior and psychological functionpsychological function

Drugs do not create behaviors outside the Drugs do not create behaviors outside the normal species-typical repertoirenormal species-typical repertoire

They alter the probability of occurrence of They alter the probability of occurrence of behaviorsbehaviors

Set and setting

The behavioral effects of drugs are due to The behavioral effects of drugs are due to complex interactions amongst the complex interactions amongst the pharmacological actions of drugs, the state pharmacological actions of drugs, the state of the organism of the organism (“set”)(“set”), and the , and the environmental circumstances surrounding environmental circumstances surrounding drug administration drug administration (“setting”)(“setting”)

Evaluating the behavioral effects of drugs

Primary EvaluationPrimary EvaluationUnconditioned effects on behaviorUnconditioned effects on behavior

Motor activityMotor activity locomotion, catalepsy, balance, strengthlocomotion, catalepsy, balance, strength

SeizuresSeizures Eating and drinkingEating and drinking

Secondary evaluation

Tests of more specific functionsTests of more specific functions(either unconditioned or conditioned (learned)(either unconditioned or conditioned (learned) AnalgesiaAnalgesia

Hot platetest

Tail-flicktest

Lightsource

Secondary evaluation

Learning and memoryLearning and memory-several different forms-several different forms

Spatial Radial Maze Task

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

Lots of spatial (room) cues

All arms baited, must not revisit arms

Rats/mice usethese cues to avoid revisitingarms (ecologicallyvalid)

•Different brain systems than non-spatial

“Win-Shift”

•Different brain systems than visible platform

•Measure latency to mount plaform & swim path (distance traveled to platform)

•Use spatial cues in room (posters, etc) to locate submerged platform (same place ea. time)

Fear and Anxiety (Mon)

Secondary Eval • Anxiety • Elevated Plus Maze

Secondary evaluation

Learning and memoryLearning and memory AnxietyAnxiety Schedule-controlled behaviorSchedule-controlled behavior

Schedules of reinforcement

Positive reinforcementPositive reinforcementPresentation Presentation increasesincreases the probability of the the probability of the preceding behaviorpreceding behavior

Negative reinforcementNegative reinforcementRemoval Removal increasesincreases the probability of the the probability of the preceding behaviorpreceding behavior

PunishmentPunishmentDecreasesDecreases the probability of a behavior the probability of a behavior

Ratio schedulesRatio schedules

Reinforcement is based in the number of Reinforcement is based in the number of responses maderesponses made

Fixed vs. variable (FR vs. VR)Fixed vs. variable (FR vs. VR)Continuous reinforcement (FR1)Continuous reinforcement (FR1)

Interval schedulesInterval schedules

Reinforcement is based on the amount of time that Reinforcement is based on the amount of time that has elapsed since the last reinforcementhas elapsed since the last reinforcement

Fixed vs. variable (FI vs. VI)Fixed vs. variable (FI vs. VI)

DRL schedules DRL schedules (differential reinforcement of low rates)(differential reinforcement of low rates)

Version of a FI; get reinforcement after fixed Version of a FI; get reinforcement after fixed time, but if respond before time is up causes time, but if respond before time is up causes “time out” and resets clock“time out” and resets clock

Schedules of reinforcement

Operant procedures used for two primary Operant procedures used for two primary reasons:reasons:

1) To ask questions about the stimulus 1) To ask questions about the stimulus properties of drugs (“what does it feel properties of drugs (“what does it feel like”)like”)

2) To ask questions about the reinforcing 2) To ask questions about the reinforcing and/or incentive properties of drugs and/or incentive properties of drugs (“will you work for it”)(“will you work for it”)

Drugs as discriminative stimuli

SSDD = stimulus that signals availability of = stimulus that signals availability of reinforcement (e.g., red vs. green light)reinforcement (e.g., red vs. green light)

Animals learn to respond when appropriate SAnimals learn to respond when appropriate SD D is is presentpresent

Drugs can serve as a SDrugs can serve as a SDD

Animals learn to respond appropriately in Animals learn to respond appropriately in presence of drug Spresence of drug SD D

SSD D is related to interoceptive cues of drugis related to interoceptive cues of drug

Drugs as discriminative stimuli

Method to ask animals about the interoceptive cues Method to ask animals about the interoceptive cues associated with different drugsassociated with different drugs

Press left lever if on morphine > get food Press left lever if on morphine > get food Right lever if given saline > get foodRight lever if given saline > get food

Give new drug - is it like morphine?Give new drug - is it like morphine? Left lever - YesLeft lever - Yes Right lever - NoRight lever - No

Drugs as discriminative stimuli

Using drug discrimination techniques find that Using drug discrimination techniques find that animals classify drugs just like humansanimals classify drugs just like humans

E.g., amphetamine and cocaine alike, but E.g., amphetamine and cocaine alike, but different than morphine, but morphine like different than morphine, but morphine like heroin and other opiatesheroin and other opiates

Measurement of drug reward

Goal is to determine abuse potential of Goal is to determine abuse potential of different drugs and to study mechanisms by different drugs and to study mechanisms by which drugs produce rewarding effects and which drugs produce rewarding effects and dependencedependence

Measure effects on withdrawal symptomsMeasure effects on withdrawal symptoms Self-administration paradigmsSelf-administration paradigms Conditional place preferenceConditional place preference

Effects on withdrawal

Steps:Steps:

Produce physical dependence with prototypical Produce physical dependence with prototypical drug (e.g., morphine)drug (e.g., morphine)

Withdraw and give unknownWithdraw and give unknown If block withdrawal symptoms will probably If block withdrawal symptoms will probably

produce similar dependence syndromeproduce similar dependence syndrome(Not conclusive)(Not conclusive)

Self-administration paradigms

Self-administration paradigms

Procedures:Procedures:

Substitution proceduresSubstitution procedures Choice proceduresChoice procedures

Predictive validity: Predictive validity: All drugs self-administered by All drugs self-administered by animals are also self-administered by people animals are also self-administered by people

Self-administration paradigms

Drugs that maintain self-administrationDrugs that maintain self-administrationamphetamines, barbiturates, cathinone, cocaine, amphetamines, barbiturates, cathinone, cocaine, codeine, ethanol, fentanyl, heroin, methadone, codeine, ethanol, fentanyl, heroin, methadone, methamphetamine, MDMA, methylphenidate, methamphetamine, MDMA, methylphenidate, morphine, nicotine, PCP, THCmorphine, nicotine, PCP, THC

Drugs that do notDrugs that do notaspirin, haloperidol, imipramine, lidocaine, aspirin, haloperidol, imipramine, lidocaine, mescaline, LSDmescaline, LSD

Self-administration paradigms

FR SchedulesFR Schedules

typical measure typical measure rate or number of rate or number of responses (or responses (or infusions)infusions)

inverted U curveinverted U curve

Sizemore et al. (1997)

Dose of Cocaine

Self-administration paradigms

FR SchedulesFR Schedules

Descending limb?Descending limb? incapacityincapacity satietysatiety loss of rewardloss of reward

Dose of Cocaine

Ascending limb Descending limb

Self-administration paradigms

FR SchedulesFR Schedules

Descending limb?Descending limb? incapacityincapacity satietysatiety loss of rewardloss of reward

Dose of CocaineSizemore et al. (1997)

Ascending limb Descending limb

Self-administration paradigms

FR SchedulesFR SchedulesOn ascending limb typically assume:On ascending limb typically assume: increase in rate = increase in rewardincrease in rate = increase in rewardOn descending limb, typically assume:On descending limb, typically assume: decrease in rate = increase in rewarddecrease in rate = increase in reward

{increase in rate = decrease in reward{increase in rate = decrease in reward(represents a compensatory response to loss of (represents a compensatory response to loss of reward)}reward)}

Self-administration paradigms

Increase in rate = decrease in rewardIncrease in rate = decrease in reward

Fits dopamine (DA) antagonist studiesFits dopamine (DA) antagonist studies DA antagonists increase rate (as does DA antagonists increase rate (as does

decreasing dose)decreasing dose)

Homepage.mac.com/sanagnos/psyc181.htmlSelf-administration paradigms

ProblemProblemE.g., 6-OHDA lesionE.g., 6-OHDA lesion

(decreased rate (decreased rate interpreted as interpreted as decreased reward)decreased reward)

Roberts et al. (1980)

Self-administration paradigms

ProblemProblem“How can both an increase and a decrease in rate of drug intake be used to draw the same conclusion? The dilemma is unmistakable: rate is an ambiguous measure of reinforcing efficacy” (Arnold & Roberts, 1997)

Self-administration paradigms

Problem of rate is Problem of rate is old issueold issue

Electrical self-stimulation

Faster rate with lower of two current intensities, but choose higher of two intensities(Hodos & Valenstein, 1962)

Self-administration paradigms(X)

Progressive ratio Progressive ratio schedulesschedules

Progressive increase Progressive increase in responses requiredin responses required1, 2, 4, 6, 9, 12, 15, 20, 25, 1, 2, 4, 6, 9, 12, 15, 20, 25, 32, 40, 50, 62, 77, 95, 118, 32, 40, 50, 62, 77, 95, 118, 145, 178, 219, 268, 328, 145, 178, 219, 268, 328, 402, 492, 603 ...402, 492, 603 ...(j = 0.20)(j = 0.20)

Self-administration paradigms

Progressive ratio Progressive ratio schedulesschedules

Measure of Measure of motivation to take motivation to take drug (how hard drug (how hard will will work for will will work for it), defined by it), defined by “breakpoint”“breakpoint”

Self-administration paradigms

““Breakpoint”Breakpoint”(highest ratio achieved)(highest ratio achieved)

“Breakpoint”

Self-administration paradigms

““Breakpoint”Breakpoint”

Comparing different drugs

DA antagonists vs. 6-OHDA

amphetaminecocaine

Self-administration paradigms

Problems: Problems: One data point, cumulative One data point, cumulative dosing, etc.dosing, etc.

Conditioned place preference

Pavlovian context conditioning procedurePavlovian context conditioning procedure Pair drug administration with place in Pair drug administration with place in

environmentenvironment Take advantage of a principle of rewardTake advantage of a principle of reward

stimuli that are rewarding, “elicit approach stimuli that are rewarding, “elicit approach responses and maintenance of contact with responses and maintenance of contact with the stimulus”the stimulus”

On test day: measure where spend timeOn test day: measure where spend time

Conditioned place preference

Conditioned place preference

AdvantagesAdvantages SimpleSimple Limited training requiredLimited training required Test in non-drug stateTest in non-drug state

DisadvantagesDisadvantages Not measure drug reward but rewarding Not measure drug reward but rewarding

properties of secondary reinforcerproperties of secondary reinforcer

Sample question

Which schedule of reinforcement is used Which schedule of reinforcement is used to calculate “breakpoint”?to calculate “breakpoint”?

(a) FR10(a) FR10(b) VI15(b) VI15(c) DRL schedule(c) DRL schedule(d) Variable ratio(d) Variable ratio(e) Progressive ratio(e) Progressive ratio