Behavioral sensitization to amphetamine in rats: changes in the rhythm of head movements during focused stereotypies

Rationale. The indirect-acting dopamine agonist amphetamine induces in rats, motor stereotypies that have served as the primary behavioral end points in studies related to schizophrenia, drug abuse, and l-dopa-induced dyskinesias. Despite the experimental importance of this rodent response to this drug, little is known about the rhythmic character of the behavior and how such rhythms change (or sensitize) in response to repeated treatment with amphetamine. Objective. To address this lack of quantitative information, the rhythms of focused stereotypies (characterized by a lack of locomotion and rapid head movements) were measured in a force-plate actometer that permitted the quantification of behavioral rhythmicity. Methods. Focused stereotypies were induced by d-amphetamine sulfate (2.5 and 5.0 mg/kg) after acute and repeated treatment with fixed doses of the drug in separate groups of rats, and the drug-induced behaviors were recorded in 1-h sessions in the actometer. Results. The two doses of amphetamine produced focused stereotypies characterized by a 10-Hz rhythm of head movements. Detailed analyses of the data for 5.0 mg/kg amphetamine showed that the rhythm in the 10-Hz region of the power spectrum increased significantly within a 1-h period, while five intermittent, repeated drug treatments significantly reduced the rhythm, possibly reflecting either tolerance or sensitization. Conclusions. Aside from providing a new quantitative approach to studying focused stereotypies, these observation direct attention to the possibility that practice-mediated processes involved in motor skill enhancement may be a part of the neural adaptations that parallel the development of sensitization to indirect-acting dopamine agonists.