Chapter 4: Methods of Research in Psychopharmacology Flashcards
What do animal evaluation techniques provide for the field of behavioural pharmacology?
- A means of quantifying animal behavior for drug testing
- Developing models for psychiatric disorders
- Evaluating the neurochemical basis of behavior
What are the advantages of animal testing?
- Having a subject population with similar genetic background and history
- Maintaining highly controlled living environments
- Being able to use invasive neurobiological techniques
- Animal subjects can be administered drugs in ways that would not be appropriate for humans
What behavioural measures of animal testing use quantitative observation?
- Motor activity
- Response to noxious stimuli
- Time spent in social interaction
What importance do operant behaviours have for animal testing?
Operant behaviors controlled by various schedules of reinforcement provide a sensitive measure of drug effects on patterns of behavior. Operant behaviors are also used in tests of addiction potential, anxiety, and analgesia.
What behavioural measures of animal testing are used to assess learning and memory?
- Classic T-maze
2. Mazes modified to target spatial learning (e.g. the radial arm maze and Morris water maze)
What behavioural measures of animal testing are used to assess working memory?
Working memory can be assessed using the delayed-response task where the animal watches a food reward get hidden somewhere (usually put in one of two boxes in front of it) but a time delay is set-up preventing the animal from immediately getting it.
What behavioural measures of animal testing are used to assess anxiety?
Many measures of anxiety use unconditioned animal reactions such as:
- the tendency to avoid brightly lit places (light–dark crossing task, open field test)
- heights (elevated plus-maze, zero maze)
- electric shock (Vogel test)
- novelty (novelty suppressed feeding)
What behavioural measures of animal testing are used to assess fear?
To assess fear a classically conditioned response is established by presenting a light or tone followed by an unavoidable foot shock. The light or tone becomes a cue associated with shock, and when presented alone, it produces physiological and behavioral responses of fearfulness. When the conditioned fear stimulus precedes a startleproducing stimulus, the startle is much greater.
What behavioural measures of animal testing are used to assess depressive behaviours?
Common measures of depressive behaviors such as the forced swim test, tail suspension test, and learned helplessness utilize acute stress to create a sense of helplessness but have been criticized for responding to acute rather than chronic antidepressant treatment. Other models of depression use more prolonged stress (chronic mild unpredictable stress, chronic social defeat stress), which more closely resembles the human experience. These stress-induced depressive behaviors respond to chronic but not acute drug treatment. Early maternal separation models the impact of stress early in life on later biobehavioral outcomes.
What behavioural measures of animal testing are used to assess anhedonia?
The sucrose preference test is a measure of anhedonia (i.e., loss of interest in normally reinforcing stimuli).
Explain the operant self-administration technique.
The operant self-administration technique, in which animals lever press for drugs rather than food reward, is an accurate predictor of abuse potential in humans. Varying the schedule of reinforcement indicates how reinforcing a given drug is, because when the effort of lever pressing exceeds the reinforcement value, the animals fail to press further (the “breaking point”). Drug self-administration can also be used to study factors leading to relapse following extinction of the drug-taking response.
Explain conditioned place preference.
In conditioned place preference, animals learn to associate a drug injection with one of two distinct compartments, and saline with the other. On test day, if the drug is rewarding, the animal spends more time in the environment associated with the drug. If aversive, the animal stays in the salineassociated environment.
Explain what discriminative stimuli in operant tasks are.
Drug effects act as discriminative stimuli in operant tasks, which means that the lever-pressing response of an animal depends on its recognizing internal cues produced by the drug. Novel drugs can be characterized by how similar their internal cues are to those of the known drug.
What is translational research?
Translational research is the interdisciplinary approach to improving the transfer of discoveries from molecular neuroscience, animal behavioral analysis, and clinical trials, with the goal of more quickly and inexpensively developing useful therapeutic drugs.
What can be done to make animal models more predictive of application to humans?
To make animal research more predictive of therapeutic benefits in humans, animal models that create abnormal behaviors or neurobiological changes that closely resemble the pathophysiology and focal symptoms of the disorder are needed. Genetic manipulations and brain lesions are two approaches for achieving this goal.
