Department of Psychology & Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Neuropsychopharmacology. 2021 Aug;46(9):1565-1573. doi: 10.1038/s41386-021-01024-3. Epub 2021 May 10.
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.
虽然冲动行为与成瘾密切相关，但这种关系的神经基础以及性别的影响尚未得到很好的描述。在这里，我们使用滴定反应时间任务来评估雄性和雌性 Long Evans 大鼠在可卡因或水/盐水自我给药（每天 6 小时）2 周后进行短期（4-6 天）或长期（25-27 天）戒断前后冲动行为的差异。在每个时间点评估了边缘前皮质（PrL）和伏隔核核心（NAc）中的神经活动。我们发现，可卡因自我给药的历史会增加所有大鼠在短期但不是长期戒断后的冲动性。此外，在任务的每个试验开始时，PrL 中兴奋神经元与抑制神经元比例增加的雄性大鼠在未接受自我给药时表现出更高的冲动性。在可卡因短期戒断后，雄性大鼠的 PrL 活动变得更加抑制，这种活动变化预测了冲动性的转变。然而，PrL 活动并不能追踪雌性大鼠的冲动性。此外，尽管 NAc 核心追踪了任务中的几个行为方面，但它并不能追踪任何性别的冲动性。总之，这些发现表明，在可卡因史前后，PrL 在冲动性方面表现出性别依赖性。
