Animal Models in Behavioural Pharmacology Flashcards
General Classification of Animal Models:
Based on operant conditioning Based on classical conditioning Based on instinctual learning (prepared associations) With demands on memory Not based on learning
Based on operant conditioning
○ Stimulus is associated with a response
○ Stimuli preceded and follow a response
○ Response is usually complex
Behaviour is goal oriented, not reflexive, easier to unlearn response
Based on classical conditioning
○ Stimuli associated with each other
○ Stimuli precedes the response
Response is typically simple/reflexive (little to no control over response, not readily changed (inflexible)
Prepared Associations
Prepared to associate certain stimuli with certain responses (i.e. easier to condition a monkey to fear a red block if it is paired with a snake than with a flower)
Not dependent on learning
○ Simpler measures (motor control, analgesia, anxiety…etc)
Need to be careful in experiments to control for confounding variable (If you want to test a drug for reduction of anxiety, but the test relies on an animals ability to learn, don’t know if drug reduces anxiety of ability to learn
Intravenous Drug Administration
Incentive Motivation (operant conditioning)
○ Used to
§ Establish reinforcing properties of drugs
§ Test rewarding properties of drugs (progressive schedule)
□ Increase number of lever presses required until rat stops responding
§ Test subjective properties of drugs (discriminative properties)
□ Train rats to lever press for food when they are on cocaine (food only available when cocaine is in their system), internal effects of cocaine becomes discriminative stimuli
□ If meth is administered, will animals still respond? Can they discriminate between internal effects?
§ Model features of addition
□ Spontaneous drug seeking
Precipitated drug seeking (previously associated cues)
Can be hard to learn, intravenous administration can lead to infection
Diagram
Intracranial drug self administration
○ Drug administered directly into brain, good for studying specific regions involved in behaviour , drug reinforcement
Too much self administration can cause a build up of pressure in the brain, results in brain regions
Intracranial self stimulation
○ Electrode used instead of an injection, planted in similar brain regions (important for reward, reinforcement)
○ Studies how much an animal will self stimulate, and if stimulation is rewarding or aversive
○ Studies interaction between stimulation of brain area with or without presence of drug
○ Used to assess reward threshold (RT)
○ RT reduced by drugs of abuse and increased by drug withdrawal (and other negative emotional states)
§ Needs lower levels of stimulation if drugs are in system
□ Effects intensified because the drug enhances the same neurotransmitter pathways that stimulation does
§ Needs higher level of stimulation if in withdrawal
Can cause lesions and seizures
Stimulus Response Learning and Memory
• Rodent touchscreen apparatus- skinner box with levers replaced with touch screen, animals nose poke the screen, hits correct response, gets food pellet
• Can record anything the rat does in the box (i.e. latency between correct response and eating food pellet) through technology
• Side that S+ appears on will change (interested in visual discrimination, not spatial learning)
• Animals start at 50% (random) slowly improve up to 85%
• Studies visual discrimination learning- animals rewarded for choosing S+, not S-
• Studies effects of drugs and lesions on acquisition or retention of simple associations
○ Can give drug daily during acquisition to see if that effects the rate of acquisition or retention
• Studies reversal learning
○ Once rats have reached asymptote (85%), switch so that S+ is now S- and vice versa, see how flexible their learning is (dependant on prefrontal cortex)
○ Good for studying neurodegenerative disorders like Alzheimer’s
Alzheimer’s patients have no problem with initial acquisition, but are impaired with reversal learning
Fear conditioning
CC
○ Aversive motivation
○ Animal model of learned anxiety and fear
○ Can be used with one trial learning, and lasts a long time
Good for studying storage of memory
Formed from Discrete CS or Contextual CS
Discrete CS
§ Single CS (i.e. tone) associated with US (.e. foot shock)
§ Play tone and give foot shock (once), freezing response develops
§ Put rat in a different box 30 days later, but even after a single pairing, if tone is presented, the rat will freeze immediately
Good way to study fear discriminative learning (amygdala dependent)
Contextual CS
§ Environment rat is in is the CS, becomes associated with shock
§ When placed in box later (no tone), rat will freeze
Requires hippocampus (integrates various aspects of environment
Place Conditioning
CC
○ Animal model of learned preference/avoidance behaviour
○ Commonly used to assess motivational properties of known or novel compounds
○ 2 distinct context are connected by a door, door closed during training
○ Inject rat with saline or drug, pair drug with one of the 2 contexts (consistent pairing between drug and one context)
○ If drug is rewarding, then if given a choice the rat will spend more time in the drug paired context (context is CS, drug is US)
§ During withdrawal, rat will spend more time in drug compartment (drug seeking behaviour)
If drug is aversive, rate will spend more time in the saline paired compartment
Diagram
Social transmission of food preference
Instinctual Learning
○ One trial test
○ Rats are social animals and learn from one another
○ Rats avoid novel foods (can’t throw up, avoid novel foods in case it is toxic)
○ Demonstrator rat is fed a novel flavour, learns it is ok
○ Demonstrator rat interacts with observer rats (hasn’t encountered the novel food before), smells the novel food on the demonstrators breath, learns that it is safe to consume
When observer rat is given a choice between 2 novel flavours, it will choose the flavour that it smelled on the demonstrator rat’s breath
Conditioned taste avoidance/aversion
Instinctual Learning
○ Pavlovian conditioning
○ Animal learns to drink from 2 water spouts
○ On training day, presented with a novel flavour (not aversive), drinks it
○ After drinking, rat injected with lithium chloride, makes them feel sick
○ Sickness is paired with novel flavour (but flavour isn’t what made them sick), can happen hours apart (prepared association)
On test day, rat given choice between water and novel flavour, will avoid novel flavour if there is a learned association between the novel flavour and sickness
