Recent work in our lab has shown that chronic stress exposure causes sex-dependent changes in subsequent relapse-like behavior in rats with a history of palatable food self-administration. Although these effects are mediated by dopamine D₁-like receptors in male rats, such dopaminergic mechanisms have not been investigated in female animals. Thus, male and female rats were trained to respond for highly palatable food reinforcers in daily sessions. During subsequent extinction training, stress was manipulated (0 or 3 h restraint/day for 7 days). To assess dopaminergic involvement, we administered either SCH-23390 (10.0 μg/kg), a dopamine D₁-like receptor antagonist, or vehicle prior to daily treatments. Rats were then tested for cue- and pellet priming-induced reinstatement. Results showed that a history of chronic stress caused an increase in pellet priming-induced reinstatement in males and a decrease in cue-induced reinstatement in females. SCH-23390 combined with stress prevented those effects in males, but not in females. In females, a history of SCH-23390 administration caused an overall increase in responding that was apparent during cue-, but not pellet priming-, induced reinstatement testing. These results establish that both the effects of chronic stress on reinstatement of food seeking and the involvement of dopamine in those effects are dependent on biological sex. Such findings should inform the development of sex-specific interventions for dietary relapse and other stress-related health problems.

我们实验室最近的工作表明，慢性压力暴露会导致具有自我管理可口食物史的大鼠随后出现类似复发的行为的性别依赖性变化。尽管这些作用是由雄性大鼠的多巴胺 D ₁样受体介导的，但尚未在雌性动物中研究过这种多巴胺能机制。因此，训练雄性和雌性大鼠在日常会话中对高度可口的食物强化剂做出反应。在随后的灭绝训练中，压力被操纵（0 或 3 小时限制/天，持续 7 天）。为了评估多巴胺能参与，我们给予 SCH-23390 (10.0 μg/kg)、多巴胺 D ₁-样受体拮抗剂，或在日常治疗前的载体。然后测试大鼠的提示和颗粒启动诱导的恢复。结果表明，慢性压力史导致雄性颗粒启动诱导恢复的增加和提示的减少- 诱导女性恢复。SCH-23390 与压力相结合可以防止这些影响在男性身上发生，但不会在女性身上发生。在女性中，SCH-23390 给药史导致响应的整体增加，这在提示诱导恢复测试中明显，但在颗粒启动诱导恢复测试中不明显。这些结果表明，慢性压力对恢复觅食的影响和多巴胺在这些影响中的参与都取决于生物性别。这些发现应该为饮食复发和其他与压力相关的健康问题的性别特异性干预措施的发展提供信息。