Effects of environmental enrichment on behavior and dopamine transporter function in medial prefrontal cortex in adult rats prenatally treated with cocaine.

The present study determined if environmental enrichment modifies the effects of prenatal cocaine on open field activity, social interaction and dopamine transporter (DAT) function in the medial prefrontal cortex (mPFC) in rats. Cocaine (40 mg/kg) or saline was administered (s.c.) to pregnant dams from gestation days 8 to 20 (PCOC and PSAL, respectively). At postnatal day 25 (PND 25), female offspring from PCOC and PSAL groups were assigned to the enriched condition (EC; PCOC/EC and PSAL/EC) or impoverished condition (IC; PCOC/IC and PSAL/IC). On PND 60, 90 and 120, locomotor activity, rearing behavior and social interactions were assessed in the open field. On PND 345, rats were anesthetized, challenged with nicotine (0.4 mg/kg), and DAT function in medial prefrontal cortex (mPFC) was assessed using in vivo voltammetry. EC groups displayed decreased locomotor activity across test days, while activity in IC groups did not habituate across days. Generally, PCOC groups displayed more rearing behavior than PSAL groups. During social interaction assessment, IC groups followed their social partner more frequently than EC groups. Moreover, the PCOC/IC group initiated more play solicitations and was engaged in mutual rearing less frequently than PCOC/EC, PSAL/IC and PSAL/EC groups, indicating that epigenetic environmental factors decreased the divergent social behaviors displayed by the PCOC/IC group. Results from in vivo voltammetry experiments demonstrated differences in baseline DAT function in response to environmental enrichment in the prenatal saline groups; however, no effect of prenatal cocaine was observed under baseline conditions. Nicotine challenge unmasked an effect of prenatal cocaine on DA clearance rate in mPFC in the IC groups, which was attenuated by environmental enrichment. Taken together, PCOC/IC rats displayed divergent social interaction and altered DAT function in mPFC, whereas the PCOC/EC group generally was not different from PSAL groups, suggesting that environmental enrichment attenuates the behavioral and neurochemical effects of prenatal cocaine.