Two dissociable components of behavioral sensitization following repeated amphetamine administration.

Abstract

The acute administration of moderate to high doses (greater than 2 mg/kg) of amphetamine (AMPH) to rats produces a multiphasic behavioral response consisting of an initial period of locomotor activity followed by episodes of intense stereotyped behavior, and a period of post-stereotype locomotion. Repeated administration of the drug results in a sensitization with two components: more rapid onset of stereotypy and enhancement of the post-stereotype locomotor activity. The studies presented below provide converging evidence that the two components of the sensitization are dissociable. 1. Rats from ten different strains or suppliers all exhibited more rapid onset of stereotypy following repeated AMPH pretreatment, whereas only five of these strains or supplier groups exhibited significantly enhanced poststereotypy locomotion. 2. The time course differed for the development of these two components of the sensitization. 3. The recovery from sensitization differed for these two components of the behavioral response. Following withdrawal of the drug, post-stereotypy motor activity diminished within 2 months while the more rapid onset of stereotypy persisted for at least 3 months. These observations have particular relevance to future studies directed at specifying the biochemical substrates of the sensitization.