Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus

Amphetamine-induced place conditioning was evaluated in mice using a newly designed apparatus. It was demonstrated that this apparatus provides a neutral set of cues devoid of rewarding or aversive properties and can reveal place preference or aversion after pairings with drugs (amphetamine and morphine for preference and naloxone for aversion) known to produce such effects. Moreover, repeated pairings of environmental cues with either 2 or 3 mg/kg d-amphetamine resulted in significant conditioned place preference on a drug free test, whilst repeated pairings with a lower dose of the drug (1 mg/kg) resulted in significant conditioned place aversion. Finally, a small number of mice showed opposite responses in comparison with group means at low as well as at high doses of amphetamine. These results suggest that amphetamine may promote conditioned place preference or avoidance depending on dosage and individual susceptibility.