Disturbance of the reciprocal-interaction between the OXTergic and DAergic systems in the CNS causes atypical social behavior in syntaxin 1A knockout mice
Disturbance of the reciprocal-interaction between the OXTergic and DAergic systems in the CNS causes atypical social behavior in syntaxin 1A knockout mice
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DOI：
10.1016/j.bbr.2021.113447
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发表时间：
2021-07-13
影响因子：
2.7
通讯作者：
Akagawa, Kimio
中科院分区：
文献类型：
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作者：
Fujiwara, Tomonori;Kofuji, Takefumi;Akagawa, Kimio
多项研究表明，催产素(Oxt)调节社会行为。同样，多巴胺(DA)等单胺类物质在调节社会行为方面也发挥着作用。以前的研究表明，可溶乙基马来酰亚胺敏感的融合附着蛋白受体(SNARE)蛋白合成素1A(STX1A)调节OXT和单胺的分泌，STX1A基因敲除(STX1AKO)小鼠表现出非典型的社会行为，如由于OXT释放减少而缺乏社会识别。本研究以STX1AKO小鼠为模型动物，分析了OXT和/或DA调节社会行为的神经机制。我们发现oxt通过oxt和V1a受体直接诱导培养的DA神经元释放DA。在STX1AKO小鼠中，OXT可部分改善小鼠的非典型社会行为，这种改善可被D1R拮抗剂所抑制。此外，通过DA再摄取抑制剂GBR12909促进DA能信号转导，STX1AKO小鼠的非典型社会行为得到部分改善。而GBR12909的改善作用可被OXTR阻断所抑制。这些结果表明，中枢神经系统中DAR能和OXT能神经元系统之间的相互作用可能在调节社会行为中起重要作用。
Several studies have shown that oxytocin (OXT) modulates social behavior. Similarly, monoamines such as dopamine (DA) play a role in regulating social behavior. Previous studies have demonstrated that the soluble Nethylmaleimide-sensitive fusion attachment protein receptor (SNARE) protein syntaxin 1A (STX1A) regulates the secretion of OXT and monoamines, and that STX1A gene knockout (STX1A KO) mice exhibit atypical social behavior, such as deficient social recognition, due to reduced OXT release. In this study, we analyzed the neural mechanism regulating social behavior by OXT and/or DA using STX1A KO mice as a model animal. We found that OXT directly induced DA release from cultured DA neurons through OXT and V1a receptors. In STX1A KO mice, the atypical social behavior was partially improved by OXT administration, which was inhibited by D1 receptor blockade. In addition, the atypical social behavior in STX1A KO mice was partially improved by facilitation of DAergic signaling with the DA reuptake inhibitor GBR12909. Moreover, the amelioration by GBR12909 was inhibited by OXTR blockade. These results suggest that the reciprocal interaction between the DAergic and OXTergic neuronal systems in the CNS may be important in regulating social behavior.