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.

Ontogeny of behavioral sensitization in the rat: effects of direct and indirect dopamine agonists

“…In the adult rat, a similar dissociation is not immediately apparent because behavioral sensitization is observed for several months after initial agonist treatments (Leith and Kuczenski 1982;Kalivas and Stewart 1991). Even so, there is other evidence indicating that the sensitization exhibited by adult rats is governed by separate processes which can be differentiated according to time since previous agonist injection.…”

“…Correspondence to: S.A. McDougall dopamine (DA) agonists and can be observed when behaviors are tested from 1 day to several months later (Wilcox et al 1980;Leith and Kuczenski 1982;Castro et al 1985;Robinson and Becker 1986;Kalivas and Stewart 1991;Mattingly et al 1991). Interestingly, the behavioral characteristics of apomorphine-and amphetamine-induced sensitization differ, perhaps indicating that these DA agonists induce sensitization via different neurobiological processes (Mattingly et al 1991;Rowlett et al 1991).…”

Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior

“…For example, when rats are sensitized to higher doses of amphetamine (e.g., 2.0 mg/kg i.p. ), they show an initial reduction in activity in response to amphetamine challenge, followed by a delayed increase in locomotor activity (Leith and Kuczenski, 1982). Behavioral sensitization can also be assessed via conditioned place preference (CPP) or drug self-administration.…”

Persistence of one-trial cocaine-induced behavioral sensitization in young rats: regional differences in Fos immunoreactivity

“…Although behavioral sensitization occurs when the psychostimulant is never associated with the testing environment (i.e., context-independent sensitization), sensitized responding is more robust when drug conditioning and testing occur in the same previously novel environment (i.e., context-dependent sensitization; Badiani et al 1997;Carey and Gui 1998;Tirelli and Terry 1998;Battisti et al 1999). In the context-dependent situation, adult rats will exhibit a sensitized response when tested even months after conclusion of repeated psychostimulant treatment (Leith and Kuczenski 1982;Hope et al 2006). Sensitization can also be observed after a single pretreatment injection of cocaine or amphetamine (i.e., a one-trial sensitization procedure); however, in using this experimental methodology, adult rats and mice only exhibit context-dependent but not context-independent behavioral sensitization (Weiss et al 1989;Fontana et al 1993;Jackson and Nutt 1993;Battisti et al 2000;McDougall et al 2007).…”