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.

中文翻译：

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性（而非青少年压力）会影响可卡因给药后的逆转学习和 DRL 表现

介绍

早期的逆境、冲动和性都会增加患药物滥用障碍的风险。我们利用大鼠研究了青少年压力如何与性和可卡因相互作用，从而影响串行逆转任务和低速率 10 秒 (DRL10) 任务的差异强化的表现。还评估了几个大脑区域中多巴胺相关蛋白的表达。

方法

从出生后 (PND) 25-29 天开始，大鼠接受可变应激方案。成年后，对大鼠进行逆转任务训练，并评估可卡因（0、10 或 20 mg/kg，IP）对表现的影响。接下来，对大鼠进行 DRL10 任务训练，并评估可卡因对表现的影响。最后，提取大脑并进行蛋白质印迹分析。

结果

青少年的压力不会影响行为。性别不会影响这两项任务的基线表现。在逆转任务中，可卡因降低了男女的高概率反应百分比和获得的奖励数量。可卡因对遗漏、低概率反应和反应潜伏期的影响具有性别依赖性。在 DRL10 任务中，可卡因降低了男女反应的峰值延迟和获得的奖励数量。可卡因对峰值响应率、响应效率、突发响应和长时间响应具有性别依赖性影响。雌性大鼠纹状体中 DRD1 受体的表达增加。

讨论

这些数据有助于越来越多的文献证明可卡因的行为影响存在性别差异，并表明 DRD1 受体可能有助于观察到的行为性别差异。