Lecture 5- Behavioural Pharmacology Flashcards
What is behavioural pharmacology
The study of the relationship between the pharmacological actions of drugs and their effects on behaviour and psychological function
Why not just experiment on humans
Largely because of more severe ethical implications, especially with drug naive subjects
What is the primary evaluation of the effects of drugs on spontaneous behaviour
Start with an observation of simple “unconditioned” behaviours
What is the secondary evaluation of the effects of drugs on spontaneous behaviour
Look at specific types of effects
What is analgesia
Pain relief
Tail flick test
-Measure time before rodent moves away from heat
-Increase with opioids
Drugs do not create
New behaviours
They alter the probability of behaviours
Rota rod test
-Tests balance and function
-Rotating rod slowly accelerates
-Measure time to fall off
Elevated puzzle maze
-Test if anxiety
-Measure the amount of time that rodents spend in exposed maze arms compared to sheltered
What is the elevated plus maze predictive of
Highly predictive of anxiolytic efficacy in humans
Radical arm maze
-Used in a variety of memory tests
-Food on one of the arms
-Change position of food after a certain amount of trials
Morris water maze
-Large tank of water in a room with external cues for navigation
-Platform to find
-Measure time finding platform, path length, % of time searching correct location
Drug discrimination
-Used to ask animals what drugs feel like
-e.g. Placebo associated with left lever
-Cocaine associated with right lever
-X drug tested, which lever
Advantages of drug discrimination
-Highly sensitive
-Accurate predictions of human subjective effects
Disadvantages of drug discrimination
-Drugs are more complex than this
-Produce different effects depending on route, dose, individual etc
Often times withdrawal symptoms are the opposite of
Drug Symptoms
Steps of comparing drugs via relief of withdrawal symptoms
-Produce physical dependence with prototypical drug
-Withdrawal and give test drug
-If that blocks withdrawal symptoms, will probably produce dependence symptoms
Criticism of comparing drugs via relief of withdrawal symptoms
Not a highly conclusive test
Positive reinforcement
Presentation increases the probability of preceding behaviour
Negative reinforcement
Removal increases the probability of a behaviour
Punishment
Presentation decreases the probability of a behaviour
A single drug can have what 3 effects all at once
-Positive reinforcement
-Negative reinforcement
-Punishment
Conditioned place preference (CPP)
-Environment that receives drugs
-Environment that receives nothing
-Animal chooses environment to be in
Advantages of CPP
-Simple
-Limited effort required
-Subjects learn quickly
-Test in non drug states
Disadvantages of CPP
-Secondary reward- not measuring drug reward itself
-Psychological and brain mechanisms poorly understood
Drugs that maintain self administration
Nearly all drugs that people abuse
Drugs that do not maintain self administration
-Hallucinogens
-Aspirin
Operant/Instrumental drug self administration
-Gold standard
-IV injections provide most precise control of dose and timing
-Oral used too
-Monkeys and humans will work for drugs
Animals do not discriminate between cocaine and
Methamphetamines
Schedules of reinforcement
-Fixed ratio
-Variable ratio
-Fixed interval
-Variable interval
Fixed ratio
-Reinforcement every n response
-eg FR1, every response, FR5, every 5 responses
-Produce steady working
Variable ratio
-Number of respondences is unpredictable but varies around some mean
-eg VR15, reinforcement on average every 15 responses (between 10-20)
Variable Interval
-Reinforcement given from first press after varying delay
-eg VI4min, reinforcement for first press after 4 min average (between 2-6)
Fixed interval
-Reinforcement given when first press after fixed delay
-eg FI2min, reinforcement for first press every 2 min
-Produce more scalloped plot
Inverted U shape curve on which schedules
‘Simple’ ratio/ interval schedules
Different doses can produce
The same response amount
How to interpret a dose response curve
-Ascending part shows decrease in responding- may indicate decrease in reinforcement
-Descending part shows decrease in responding - may indicate increase in reinforcement
Criticism of self administration
-Rate of responding on simple FR is an ambiguous measure
-Many factors of the drug determine response rate, not just rewarding effects
-eg motor side effects of drug, satiation effects etc
What is progressive ratio schedules
-Exponential increase in number of responses required for drug
-Breakpoint, highest ratio before giving up, measure of drug motivation
Advantage of progressive ratio schedules
-Much less drug is consumed
-Lower chance of motor and satiation side effects
-However may produce extinction of learning
What’s second order schedules
-Light associated with drug
-Press the lever till the light shows then press till drug is administered
-Can support large amounts of lever pressing with little or no drug in system
Stimuli that’s reinstate responding
-Drug itself
-Drug cue
-Drug context
-Stress
Test for relapse/reinstatement
-Extinguish responding
-Present stimulus and see if reinstate responding
Self administration is not enough to show
Addiction
“Extended access” models
-One group of rats allowed to self-administer for short period (ShA)
-Other group for long (LgA)
-First hour intake similar
-Escalated use in long access