Effects of differential rearing on amphetamine-induced c-fos expression in rats.

BACKGROUND Rearing rats in environmental enrichment alters psychostimulant-induced locomotor activity as well as neurotransmitter expression. Exposure to novelty and psychostimulants induces c-fos expression in neurons in the mesolimbic dopamine (DA) pathway. Here we investigated changes in the expression of the immediate early gene c-fos in the mesolimbic DA pathway of enriched, isolated, or socially reared rats due to the neurobiological changes that result from rearing conditions and influence drug taking behavior. METHODS Rats were reared in either enriched (EC), isolated (IC), or social (SC) conditions for 30 days, after which they received an acute amphetamine or saline injection (1.0 mg/kg) and locomotor activity was measured. Following immunohistochemical staining c-fos positive neurons were quantified in the NAcc, mPFC, and amygdala. RESULTS Greater locomotor activity was observed in differentially reared rats treated with amphetamine compared to saline, as well as in SC compared to EC and IC rats. Rats reared in an IC context demonstrated greater c-fos expression than EC rats in the NAcc when treated with amphetamine, and EC saline rats demonstrated greater c-fos expression in the cingulate and prelimbic cortices compared to SC saline rats. Additionally, IC amphetamine rats displayed greater c-fos expression in the NAcc compared to IC saline rats, while EC saline rats displayed greater c-fos expression in the prelimbic cortex compared to EC amphetamine rats. CONCLUSIONS These results suggest regional specificity of psychostimulant-induced c-fos expression in the prelimbic/NAcc pathway that is altered in differential rearing, and influences initial c-fos activation following psychostimulant exposure.