Sex, but not juvenile stress, affects reversal learning and DRL performance following cocaine administration

Introduction

Early adversity, impulsivity and sex all contribute to the risk of developing substance use disorder. Using rats, we examined how juvenile stress interacts with sex and cocaine to affect performance on a serial reversal task and a differential reinforcement of low rates 10 s (DRL10) task. The expression of dopamine-related proteins in several brain areas was also assessed.

Methods

From postnatal days (PND) 25–29, rats were exposed to a variable stress protocol. In adulthood, rats were trained on the reversal task and the effects of cocaine (0, 10, or 20 mg/kg, IP) on performance were assessed. Next, rats were trained on the DRL10 task and the effects of cocaine on performance were assessed. Finally, brains were extracted, and Western blot analyses conducted.

Results

Juvenile stress did not affect behavior. Sex did not affect baseline performance in either task. In the reversal task, cocaine decreased % high probability responses and the number of rewards earned in both sexes. Cocaine had sex-dependent effects on omissions, low probability responses and response latencies. In the DRL10 task, cocaine decreased the peak latency to respond and the number of rewards earned in both sexes. Cocaine had sex-dependent effects on peak rate of responding, response efficiency, burst responses and long responses. Female rats exhibited increased expression of DRD1 receptors in the striatum.

Discussion

These data contribute to the growing literature demonstrating sex differences in the behavioral effects of cocaine and suggest that DRD1 receptors could contribute to the observed behavioral sex differences.