Effects of environmental enrichment on cocaine-seeking behavior in female rats and RNA expression in the Nucleus Accumbens

Substance abuse disorder is a debilitating condition characterized by recurring drug-seeking behaviors and high rates of relapse. In male rats, this tendency to engage in drug-seeking behavior can be inhibited by environmental enrichment (EE) during abstinence. We have shown previously that cocaine-seeking behavior is associated with an increase in addiction-related genes such as Arc and CamkIIa and a decrease in the microRNA miR-495. We have also shown that miR-495 inhibits expression of Arc and CamkIIa post-transcriptionally. Therefore, we hypothesize that reduced cocaine-seeking behavior in EE female rats is associated with a downregulation of these addiction-related genes as well as an upregulation of miR-495 in the NAc shell. Based on previous studies that highlight differences between male and female motivation for cocaine, we also hypothesize that EE will not affect female motivation for cocaine as robustly as males. After acquiring cocaine through self-administration, females were assigned to either an enriched environment (EE) condition or an isolated condition, where they remained during abstinence. They were then given a one-hour cue-reactivity test, during which cocaine-seeking behavior differed significantly between the EE and isolated groups. We also found that the addiction-related genes Arc and CamkIIa were downregulated in the NAc core of EE females. Future research is needed to examine the role of miR-495 in these changes in behavior and gene expression. Overall, the results suggest that EE is protective against relapse to cocaine-seeking in females and may normalize the dysregulation of genes by cocaine.