Reverse tolerance to amphetamine of mice bearing unilateral striatal lesions: effect upon the circling response to apomorphine

Abstract

When mice bearing unilateral lesions of the striatum receive weekly doses of amphetamine, their circling responses increase with successive doses, i.e., they become reverse tolerant (1). The present work was undertaken to ascertain whether presynaptic dopaminergic changes might underlie this phenomenon. This was approached by observing whether the response to a direct dopaminergic agent would be affected by the development of reverse tolerance to amphetamine. The circling responses of unilaterally electrothermally lesioned mice to apomorphine, 0.4 mg/kg s.c., increased significantly after four weekly 4 mg/kg s.c. doses of d-amphetamine. The responses to apomorphine of mice not exposed to amphetamine declined over the same interval. The conclusion drawn is that presynaptic effects are not likely to underlie the phenomenon of reverse tolerance.