Abstract
These studies determined whether differential rearing alters the corticosterone diurnal cycle in rats and whether differential rearing alters the corticosterone response to amphetamine treatment. The studies also determined whether blocking the glucocorticoid receptor differentially alters low dose amphetamine self-administration in differentially-reared rats. Male Sprague-Dawley rats were raised in either an enriched condition (EC), standard condition (SC) or an isolated condition (IC). Rats were then implanted with an intravenous catheter which allowed for blood collections. Following recovery and habituation to the blood collection procedure, blood samples were collected across six time points within a 24 hr period. Following the collection of the blood samples, rats were treated with one of three dose of amphetamine (0, 0.5, and 2.0 mg/kg) and blood samples were collected. In a different experiment, EC and IC rats acquired amphetamine self-administration across seven days at a dose of 0.1 mg/kg/infusion. Following the seven days of acquisition, EC and IC rats were separated into one of two groups; one group was switched to a high dose of amphetamine (0.03 mg/kg/infusion) and the other group was switched to a low dose of amphetamine (0.003 mg/kg/infusion). Once drug intake was stable, rats received 45-min pretreatments with varying doses of the glucocorticoid receptor antagonist RU-486 (0, 5, 10, and 20 mg/kg). IC rats had significantly higher corticosterone levels at two time points during the light phase compared to the EC rats. Fifteen minutes following treatment with both 0.5 and 2.0 mg/kg amphetamine, IC rats had higher corticosterone levels than both EC and SC rats. Pretreatments with the highest dose of RU-486 resulted in less of a decrease in high dose amphetamine self-administration in IC rats compared to low dose amphetamine self-administration in IC rats. The results from these studies indicate that the differential rearing in IC rats results in an overactive stress axis. This overactive stress axis may be playing a role in the greater behavioral sensitivity to amphetamine found in IC rats. Keywords: Enrichment, Corticosterone, Amphetamine Self-Administration, Rats, Stress.