Enrichment-induced differences in methamphetamine drug discrimination in male rats

Abstract

Rats raised in an enriched environment show a decrease in sensitivity to the subjective effects of the psychostimulant d-amphetamine. The purpose of the present study was to determine if environmental enrichment during development alters the subjective effects of the more commonly abused drug methamphetamine. Male Sprague-Dawley rats were raised in either an enriched (EC) or an isolated condition (IC). EC and IC rats were trained on a two-lever operant procedure to discriminate 1.0 mg/kg (i.p.) methamphetamine from saline. Following acquisition of the discrimination a methamphetamine generalization curve (0.1–1.0 mg/kg) was determined. The antagonistic effects of dopamine D1 receptor antagonist SCH23390 (0.0075–0.06 mg/kg) and the dopamine D2 receptor antagonist eticlopride (0.01–0.3 mg/kg) were also tested. Finally, the ability of nicotine (0.05–0.5 mg/kg) to generalize and the ability of the nicotinic receptor antagonist mecamylamine (0.125–0.5 mg/kg) to antagonize the discriminative stimulus effects of methamphetamine were determined. EC rats were less sensitive to discriminative stimulus effects of methamphetamine compared to IC rats at a low 0.3 mg/kg dose and showed full antagonism of methamphetamine discrimination following SCH23390 compared to IC rats. There were no environmentally-induced differences in the effects of eticlopride. Nicotine only partially generalized to the effects of methamphetamine in both EC and IC rats. While mecamylamine failed to antagonize the effects of methamphetamine in either EC or IC rats. These results suggest that environmental enrichment decreases sensitivity to the discriminative effects of methamphetamine and the differences may be mediated through changes in the D1 dopamine receptor.