Heightened risk-based decision-making is observed across several neuropsychiatric disorders including schizophrenia, bipolar disorder, and Parkinson's disease, yet no treatments exist that effectively normalize this aberrant behavior. Preclinical risk-based decision-making paradigms have identified the important modulatory roles of dopamine and sex in the performance of such tasks, though specific task parameters may alter such effects (e.g., punishment and reward values). Previous work has highlighted the role of dopamine 2-like receptors (D2R) during performance of the Risk Preference Task (RPT) in male rats, however sex was not considered as a factor in this study, nor were treatments identified that reduced risk preference. Here, we utilized the RPT to determine sex-dependent differences in baseline performance and impact of the D2R receptor agonist pramipexole (PPX), and antagonist sulpiride (SUL) on behavioral performance. Female rats exhibited heightened risk-preference during baseline testing. Consistent with human studies, PPX increased risk-preference across sex, though the effects of PPX were more pronounced in female animals. Importantly, SUL reduced risk-preference in these rats across sexes. Thus, under the task specifications of the RPT that does not include punishment, female rats were more risk-preferring and required higher PPX doses to promote risky choices compared to males. Furthermore, blockade of D2R receptors may reduce risk-preference of rats, though further studies are required.

中文翻译：

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大鼠基于风险的决策的性别差异以及多巴胺2样受体对风险偏好的调节

在精神分裂症、双相情感障碍和帕金森病等多种神经精神疾病中观察到基于风险的决策增强，但尚无有效使这种异常行为正常化的治疗方法。临床前基于风险的决策范式已经确定了多巴胺和性别在执行此类任务中的重要调节作用，尽管特定的任务参数可能会改变此类效果（例如，惩罚和奖励值）。先前的工作强调了多巴胺 2 样受体 (D2R) 在雄性大鼠执行风险偏好任务 (RPT) 过程中的作用，但本研究并未将性别视为一个因素，也没有发现可降低风险偏好的治疗方法。在这里，我们利用 RPT 来确定基线表现的性别依赖性差异以及 D2R 受体激动剂普拉克索 (PPX) 和拮抗剂舒必利 (SUL) 对行为表现的影响。雌性大鼠在基线测试期间表现出更高的风险偏好。与人类研究一致，PPX 增加了不同性别的风险偏好，尽管 PPX 的影响在雌性动物中更为明显。重要的是，SUL 降低了这些不同性别大鼠的风险偏好。因此，在不包括惩罚的 RPT 任务规范下，与雄性大鼠相比，雌性大鼠更倾向于风险，并且需要更高的 PPX 剂量来促进风险选择。此外，阻断 D2R 受体可能会降低大鼠的风险偏好，但还需要进一步研究。