A sex-dependent role for the prelimbic cortex in impulsive action both before and following early cocaine abstinence.

Although impulsive action is strongly associated with addiction, the neural underpinnings of this relationship and how they are influenced by sex have not been well characterized. Here, we used a titrating reaction time task to assess differences in impulsive action in male and female Long Evans rats both before and after short (4-6 days) or long (25-27 days) abstinence from 2 weeks of cocaine or water/saline self-administration (6 h daily access). Neural activity in the prelimbic cortex (PrL) and nucleus accumbens (NAc) core was assessed at each time point. We found that a history of cocaine self-administration increased impulsivity in all rats following short, but not long, abstinence. Furthermore, male rats with an increased ratio of excited to inhibited neurons in the PrL at the start of each trial in the task exhibited higher impulsivity in the naïve state (before self-administration). Following short abstinence from cocaine, PrL activity in males became more inhibited, and this change in activity predicted the shift in impulsivity. However, PrL activity did not track impulsivity in female rats. Additionally, although the NAc core tracked several aspects of behavior in the task, it did not track impulsivity in either sex. Together, these findings demonstrate a sex-dependent role for the PrL in impulsivity both before and after a history of cocaine.