Context-dependent cross-sensitization between cocaine and amphetamine.

We investigated the effect of amphetamine pretreatment on the locomotor response to subsequent cocaine challenge. Rats were administered either 0.75 mg/kg amphetamine in a testing environment and saline in their home cage, saline in the testing environment and 0.75 mg/kg amphetamine in their home cage, or saline in both the testing environment and home cage. After 5 pairings of drug to environment, conditioning was tested by administration of a saline injection. Both amphetamine treated groups exhibited increased locomotion in response to saline injection. After the eighth session of the pairing regimen, all animals were administered 5 mg/kg cocaine in the test environment and their behavior measured for 30 min. Sensitization to cocaine was observed only in rats with previous amphetamine exposure in the testing environment. There was no difference between groups in whole brain, striatal, or plasma levels of cocaine. The data support the hypothesis that sensitization is independent of brain cocaine levels.