Summary of Animal Models of the Withdrawal/Negative Affect Stage

Motivational measures of drug withdrawal have significant face validity for the motivational measures of drug withdrawal in humans. Dysphoria, hypohedonia, loss of motivation, anxiety, and irritability can all be reflected in the animal models described above. ICSS threshold procedures also have high predictive validity for changes in the reward value of the drug. The disruption of operant responding during drug abstinence reflects general malaise. Drug discrimination allows a powerful and sensitive comparison to other drug states. Conditioned place aversion reflects an aversive unconditioned stimulus. The escalation of intake of all drugs of abuse is also associated with an increased breakpoint on a progressive-ratio schedule, indicating that animals will work harder to obtain the drug – possibly reflecting either enhanced motivation to seek the drug or the enhanced reward value of the drug, or both.

As more and more data are generated that establish the neurobiological bases of negative emotional states in animals that correspond to such negative emotional states in humans, these measures will gain construct validity (Koob and Volkow, 2010). The use of multiple dependent variables in studies of the motivational effects of withdrawal reveal numerous overlapping neurobiological substrates, laying a framework for identifying the counteradaptive mechanisms that drive addiction. The reinforcing value of drugs may change as an individual becomes dependent. The neurobiological basis for such changes is only beginning to be investigated. Thus, drug dependence can produce an aversive or negative motivational state, manifested by changes in numerous behavioral measures, such as response disruption, changes in reward thresholds, and conditioned place aversions.

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