Importance of environmental context in the development of amphetamine- or apomorphine-induced stereotyped behavior after single and multiple doses

The present study was designed to determine whether single and repeated pre treatment regimens with amphetamine or apomorphine differ in the context-de pendency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg intraperitonea lly [IP]) or apomorphine (40 mg/kg subcutaneously [SC]) only became sensiti zed to a lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/k g SC) when placed in an environment that was the same as the pretreatment e nvironment. However, animals pretreated with 3 high doses (24-h apart) of a mphetamine (14 mg/kg IP) or apomorphine (40 mg/kg SC) did demonstrate sensi tization to a lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when placed in an environment that was different from the pretre atment environment. Context-dependent sensitization, but not context-indepe ndent sensitization; was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determine d that neither sensitization model could be related to pharmacokinetic fact ors. Therefore, the results indicate that repeated exposure to amphetamine or apomorphine overcomes the context-dependent component of sensitization o f amphetamine- or apomorphine-induced stereotyped behavior. (C) 2000 Elsevi er Science Inc.