The impact of early environmental rearing condition on the discriminative stimulus effects and Fos expression induced by cocaine in adult male and female rats

Rationale: A number of environmental manipulations, including maternal separation (MS), have been shown to alter behavioral responses to drugs of abuse. Objectives: This study assessed if MS affected the stimulus and Fos-inducing effects of cocaine. Materials and methods: In experiment 1, male and female Sprague-Dawley rats were exposed to brief maternal separations (BMS), long maternal separations (LMS), or animal facility rearing (AFR) and then trained as adults to discriminate cocaine (10 mg/kg, intraperitoneally) from saline. Following training, generalization tests to novel doses of cocaine and other dopaminergic compounds were performed. Assessments of variations in training dose pretreatment times were also made. In experiment 2, male and female rats exposed to MS conditions were administered cocaine or saline for 14 days, and Fos expression in the mesolimbic system was measured. Results: In males, BMS retarded the acquisition of the cocaine discrimination. Generalization to novel doses of cocaine did not differ among rearing conditions, but the training dose cue lasted longer in LMS. Distinct generalization and ED₅₀ profiles were found between male rearing conditions for all dopamine compounds. While BMS females had higher cocaine ED₅₀ estimates, no other differences were found in females. LMS males and females, as well as AFR females, had significant increases in Fos expression after cocaine in a region-specific manner. No differences were found with other rearing groups. Conclusion: Early environmental variables altered the stimulus effects (in a sex-dependent manner) as well as the neuronal responsiveness to cocaine, which may be mediated by the dopamine system.