Effects of social defeat on dopamine neurons in the ventral tegmental area in male and female California mice.
Effects of social defeat on dopamine neurons in the ventral tegmental area in male and female California mice.
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DOI：
10.1111/ejn.13099
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发表时间：
2015-12
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影响因子：
--
通讯作者：
Trainor BC
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文献类型：
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作者：
Greenberg GD;Steinman MQ;Doig IE;Hao R;Trainor BC
腹侧被盖区（VTA）的多巴胺神经元具有与奖励相关的重要功能，但在厌恶的环境中也会被激活。电生理学研究表明，VTA 多巴胺神经元对有害刺激的反应程度是在背腹范围内按地形组织的。我们使用 c-fos 免疫组织化学来检查 VTA 多巴胺神经元在社交失败和社交方式背景下的反应。通过研究一夫一妻制的加州小鼠（Peromyscus californicus），我们能够观察到社交失败对雄性和雌性的影响。与对照组相比，经历过 3 次失败（而非单次失败）的雌性腹侧（而非背侧）VTA 中酪氨酸羟化酶 (TH)/c-fos 阳性细胞更多。这一观察结果表明，反复暴露于厌恶的环境中对于触发 VTA 多巴胺神经元的激活是必要的。失败并不影响雄性中 TH/c-fos 的共定位。我们还在社交互动测试中研究了失败对 c-fos 表达的长期影响。正如之前报道的那样，失败会减少女性的社交互动，但不会减少男性的社交互动。令人惊讶的是，失败压力对 VTA 任何分区的 TH/c-fos 共定位没有影响。然而，在整个 VTA 中，雌性比雄性具有更多的 TH/c-fos 阳性细胞，并且在伏隔核 (NAc) 壳的后亚区域也具有更多的 c-fos 阳性细胞计数。我们的结果表明，VTA 中的多巴胺神经元对女性的社交环境更加敏感，并且腹侧 VTA 对厌恶环境尤其敏感。
Dopamine neurons in the ventral tegmental area (VTA) have important functions related to rewards but are also activated in aversive contexts. Electrophysiology studies suggest that the degree to which VTA dopamine neurons respond to noxious stimuli is topographically organized across the dorsal-ventral extent. We used c-fos immunohistochemistry to examine the responses of VTA dopamine neurons in contexts of social defeat and social approach. Studying monogamous California mice (Peromyscus californicus) allowed us to observe the effects of social defeat on both males and females. Females exposed to three episodes of defeat, but not a single episode, had more tyrosine hydroxylase (TH)/c-fos positive cells in ventral (but not dorsal) VTA compared to controls. This observation suggests that repeated exposure to aversive contexts is necessary to trigger activation of VTA dopamine neurons. Defeat did not affect TH/c-fos colocalizations in males. We also examined long term effects of defeat on c-fos expression in a social interaction test. As previously reported, defeat reduced social interaction in females but not males. Surprisingly, there were no effects of defeat stress on TH/c-fos colocalizations in any subregion of the VTA. However, females had more TH/c-fos positive cells than males across the entire VTA, and also had greater c-fos positive cell counts in posterior subregions of the nucleus accumbens (NAc) shell. Our results show that dopamine neurons in the VTA are more responsive to social contexts in females and that the ventral VTA in particular is sensitive to aversive contexts.