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 d ependency of sensitization of stereotyped behavior. Male CF-1 mice that wer e pretreated with a single high dose of amphetamine (14 mg/kg, IF) or apomo rphine (40 mg/kg, SC) only became sensitized to a lower test dose of amphet amine (7 mg/kg, IF) or apomorphine (3 mg/kg, SC) when placed in an environm ent that was the same as the pretreatment environment. However, animals pre treated with three high doses (24 h apart) of amphetamine (14 mg/kg, IF) or apomorphine (40 mg/kg, SC) did demonstrate sensitization to a lower test d ose of amphetamine (7 mg/kg, IF) or apomorphine (3 mg/kg, SC) when placed i n an environment that was different from the pretreatment environment. Cont ext-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instea d of drug injections. In addition, it was determined that neither sensitiza tion model could be related to pharmacokinetic factors. Therefore, the resu lts indicate that repeated exposure to amphetamine or apomorphine overcomes the context-dependent component of sensitization of amphetamine- or apomor phine-induced stereotyped behavior. (C) 2000 Elsevier Science Inc.