Critical issues in assessing the behavioral effects of amphetamine.

Amphetamine induces a behavioral syndrome in mammals that includes a variety of repetitive behaviors. An integral component of this syndrome in humans is the presence of a thought disturbance not unlike that manifest in idiopathic paranoid schizophrenia. The consistent pattern of behavioral changes produced by amphetamine across species, when considered in light of the psychosis it elicits in humans, has suggested to many that these drug-induced changes in animals may provide a model of the endogenous psychosis in humans. Amphetamine-induced changes in open-field behavior in the rat have been the most widely studied in attempts to formulate a model for investigating the neurobiological mechanisms underlying amphetamine psychosis and paranoid schizophrenia in humans and for testing the therapeutic efficacy of new antipsychotic drugs. The procedures used to assess the behavioral response to amphetamine, however, typically include rating scales or automated recordings that by their very nature ignore those components of the behavioral response that may be most critical for developing a viable animal model of the naturally occurring psychosis. Further, open-field behavior is often recorded during arbitrarily selected intervals without consideration for the multiphasic nature of the entire amphetamine response. We discuss how incomplete descriptive analyses of the amphetamine behavioral response in rats has led to confusion in the literature and describe behavioral research that is paradigmatic of the work we believe is most likely to eventuate in significant progress in the field.