Sex differences in effects of dopamine D1 receptors on social withdrawal.
Sex differences in effects of dopamine D1 receptors on social withdrawal.
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DOI：
10.1016/j.neuropharm.2013.09.026
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发表时间：
2014-02
影响因子：
4.7
通讯作者：
Trainor BC
中科院分区：
文献类型：
--
作者：
Campi KL;Greenberg GD;Kapoor A;Ziegler TE;Trainor BC
多巴胺信号在运动状态的调节中起着重要的作用。最近在雄性啮齿动物中的研究表明，社交失败压力增加了投射到NAc的腹侧被盖多巴胺神经元的活性，并且这种增加的活性对于压力诱导的社交退缩是必要的。国内的雌性小鼠没有类似的攻击性，这阻碍了对雌性小鼠的补充研究。使用一夫一妻制的加州小鼠（Peromyscus californicus），我们发现，社会失败增加总多巴胺，DOPAC，和HVA含量在NAC在男性和女性。这些结果与之前在小鼠中的研究基本一致，并表明失败压力也会增加女性的NAc多巴胺信号。然而，这些结果并不能解释我们先前的观察，即失败压力诱导雌性而不是雄性加州小鼠的社交退缩。药理学操作提供了更多的见解。当500 ng的D1激动剂SKF38393被注入到未被打败的雌性的NAc壳中时，社会互动行为减少。相同剂量的SKF38393对雄性动物无影响，表明D1受体激活足以诱导雌性动物而非雄性动物的社交退缩。D1拮抗剂SCH 23390的内注射增加了女性暴露于失败的社会接近行为，但不是在女性天真的失败。这一结果表明，D1受体是必要的失败引起的社会退缩。总的来说，我们的研究结果表明，由D1受体调节的分子途径的性别差异有助于社会退缩行为的性别差异。
Dopamine signaling in the nucleus accumbens (NAc) plays a critical role in the regulation of motivational states. Recent studies in male rodents show that social defeat stress increases the activity of ventral tegmental dopamine neurons projecting to the NAc, and that this increased activity is necessary for stress-induced social withdrawal. Domestic female mice are not similarly aggressive, which has hindered complementary studies in females. Using the monogamous California mouse (Peromyscus californicus), we found that social defeat increased total dopamine, DOPAC, and HVA content in the NAc in both males and females. These results are generally consistent with previous studies in Mus, and suggest defeat stress also increases NAc dopamine signaling in females. However, these results do not explain our previous observations that defeat stress induces social withdrawal in female but not male California mice. Pharmacological manipulations provided more insights. When 500 ng of the D1 agonist SKF38393 was infused in the NAc shell of females that were naïve to defeat, social interaction behavior was reduced. This same dose of SKF38393 had no effect in males, suggesting that D1 receptor activation is sufficient to induce social withdrawal in females but not males. Intra-accumbens infusion of the D1 antagonist SCH23390 increased social approach behavior in females exposed to defeat but not in females naïve to defeat. This result suggests that D1 receptors are necessary for defeat-induced social withdrawal. Overall, our results suggest that sex differences in molecular pathways that are regulated by D1 receptors contribute to sex differences in social withdrawal behavior.
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