Rationale

Depressed individuals demonstrate debilitating symptoms, including depressed mood, anhedonia, and effort-related deficits. Effort-related decision-making can be measured through providing subjects with a choice between high effort/reward and low effort/reward options, which is a dopamine (DA)–dependent behavior. While previous research has shown sex differences in depression rates, this has not been examined within operant-based effort-related decision-making tasks nor has DA been shown to underlie this behavior in female rats.

Objectives

The current study investigated sex differences in an effort-related decision-making task prior to and following administration of the DA D2 receptor antagonist haloperidol (HAL).

Methods

Adult rats were food restricted or fed freely and trained in an effort-related progressive ratio choice task. After stable responding, HAL was administered acutely (0.05–0.2 mg/kg) prior to testing.

Results

Results indicate a significant effect of sex on training variables, with males having a greater number of lever presses, higher ratios, and longer active lever times. Pretreatment with HAL significantly reduced the same measures in both sexes for the high-valued reward, while increasing chow consumption in the food restricted males. Food restricted rats showed a greater number of total lever presses and achieved higher ratios; however, the effect in male food restricted rats was greatest.

Conclusions

These data suggest that, although there are sex differences in training, HAL decreases behavior across sexes, demonstrating that the D2 mechanism is similar in both sexes. These findings provide a better understanding of motivational dysfunction in both sexes and potential treatment targets for depression.

中文翻译：

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努力相关决策中的性别差异：多巴胺D2受体拮抗作用

基本原理

沮丧的人表现出令人衰弱的症状，包括情绪低落，快感不足和与工作有关的缺陷。与工作量有关的决策可以通过向受试者提供在高努力/奖励和低努力/奖励选项之间进行选择来衡量，这是一种依赖多巴胺（DA）的行为。尽管先前的研究表明抑郁症的性别存在差异，但尚未在基于操作员的与努力相关的决策任务中对此进行检查，也未发现DA是雌性大鼠这种行为的基础。

目标

本研究调查了DA D2受体拮抗剂氟哌啶醇（HAL）给药前后与努力相关的决策任务中的性别差异。

方法

成年大鼠受到食物限制或自由进食，并接受了与工作有关的渐进式比例选择任务的训练。稳定的反应后，在测试前急性给予HAL（0.05–0.2 mg / kg）。

结果

结果表明，性别对训练变量有显着影响，男性的杠杆按下次数更多，比率更高，有效杠杆操作时间更长。用HAL预处理显着减少了男女双方获得高价值报酬的相同措施，同时增加了受食物限制的男性的食物消耗。食物受限的大鼠显示出更多的总杠杆按压，并且获得了更高的比率。然而，在限制雄性食物的大鼠中效果最大。

结论

这些数据表明，尽管在训练中存在性别差异，但是HAL会降低性别之间的行为，表明D2机制在两个性别上都是相似的。这些发现提供了对男女动机障碍和抑郁症潜在治疗目标的更好理解。