Apparent tolerance to some aspects of amphetamine stereotypy with long-term treatment

Abstract

Previous reports have demonstrated that long-term amphetamine treatment results in a progressive augmentation of locomotion and focused stereotypy in the rat. A series of experiments were conducted to determine whether an increase in dopamine receptor sensitivity is the primary mechanism underlying the behavioral alterations associated with multiple amphetamine injections. Detailed observations of the focused stereotyped behaviors produced by amphetamine revealed that although some components were enhanced with long-term treatment, others were reduced. Thus, whereas repeated administration of 2.5 mg/kg d-amphetamine produced a progressive increase in repetitive head and limb movements, long-term treatment with 5.5 mg/kg d-amphetamine resulted in a reduction of licking and biting behaviors (oral stereotypies). These results, which suggest that different mechanisms mediate the various components of focused stereotypy, argue against the supersensitivity hypothesis. In fact, the apparent tolerance that develops to oral stereotypies may reflect a decrease in dopamine receptor sensitivity since repeated amphetamine administration also reduces the oral stereotypies produced by 0.5 or 2.0 mg/kg apomorphine, a direct acting dopamine agonist. Thus, the behavioral alterations produced by repeated amphetamine injections cannot be explained solely by an increase in receptor sensitivity.