Animal Models of the Preoccupation/Anticipation Stage of the Addiction Cycle

Summary of Animal Models of the Preoccupation/Anticipation Stage

Each of the models of this stage of the addiction cycle has face validity with the human condition, and all provide frameworks for understanding the neurobiological bases of various aspects of craving. The DSM-IV criteria that apply to the craving stage and loss of control over drug intake include “any unsuccessful effort or persistent desire to cut down or control substance use.”

Second-order schedules of reinforcement can assess the motivational value of a drug in the absence of the drug’s acute effects that could otherwise influence performance or processes that can interfere with motivational function. Reinstatement models have demonstrated face validity, but their predictive validity remains to be established, with little evidence of predictive validity from studies of pharmacological treatments for drug relapse. Very few clinical trials have tested medications that effectively prevent reinstatement, and very few anti-relapse medications that have been tested in animal models of reinstatement have had success in human laboratory studies or clinical trials. However, drug re-exposure or priming, stressors, and cues paired with drugs all produce reinstatement in animal models and promote relapse in humans, providing some support for the functional equivalence and construct validity of these modes.

A challenge for future studies will be to develop cross-species endophenotypes, from animals to humans, which will allow further construct validity and functional equivalence in studies of genetic and environmental vulnerability and the neurobiological mechanisms therein.

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