AIM Astroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the role of these proteins in response to currently available psychotropic drugs is still unknown. METHODS To investigate this, we evaluated the behavioural effects of the genetic and pharmacological inactivation of Cx43 on the antidepressant- and anxiolytic-like activities of the selective serotonin reuptake inhibitor fluoxetine and the benzodiazepine diazepam, respectively. RESULTS A single administration of fluoxetine (18 mg/kg; i.p.) produced a higher increase in hippocampal extracellular serotonin levels, and a greater antidepressant-like effect in the tail suspension test in Cx43 knock-down (KD) mice bred on a C57BL/6 background compared to their wild-type littermates. Similarly, in outbred Swiss wild-type mice, the intra-hippocampal injection of a shRNA-Cx43 or the acute systemic injection of the Cxs inhibitor carbenoxolone (CBX: 10 mg/kg; i.p.) potentiated the antidepressant-like effects of fluoxetine. Evaluating the effects of such strategies on diazepam (0.5 mg/kg; i.p.), the results indicate that Cx43 KD mice or wild-types injected with a shRNA-Cx43 in the amygdala, but not in the hippocampus, attenuated the anxiolytic-like effects of this benzodiazepine in the elevated plus maze. The chronic systemic administration of CBX mimicked the latter observations. CONCLUSION Collectively, these data pave the way to the development of potentiating strategies in the field of psychiatry based on the modulation of astroglial Cx43.

中文翻译：

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星形胶质连接蛋白43的遗传和药理失活差异地影响抗抑郁药和抗焦虑药的急性反应。

AIM星形胶质连接蛋白（Cx）30和43参与间隙连接和半通道活动。有证据表明这些功能实体有助于调节神经传递，从而影响大脑功能。特别是，临床前和临床发现突出了Cx43在抑郁动物模型中的作用。然而，这些蛋白在响应目前可用的精神药物中的作用仍是未知的。方法为了对此进行调查，我们评估了Cx43的遗传和药理失活对选择性5-羟色胺再摄取抑制剂氟西汀和苯并二氮杂地西epa的抗抑郁和抗焦虑活性的行为影响。结果单次服用氟西汀（18 mg / kg; ip）可使海马细胞外血清素水平升高，与野生型同窝仔相比，在以C57BL / 6背景饲养的Cx43敲低（KD）小鼠的尾部悬吊试验中，其抗抑郁样作用更大。类似地，在瑞士野生近交小鼠中，海马内注射shRNA-Cx43或急性全身注射Cxs抑制剂羧苄酮（CBX：10 mg / kg；腹膜内）可增强氟西汀的抗抑郁样作用。评估此类策略对地西epa（0.5 mg / kg;腹膜内）的影响，结果表明，在杏仁核而非海马中注射shRNA-Cx43的Cx43 KD小鼠或野生型减弱了抗焦虑作用。高架迷宫中的这种苯二氮卓类药物。CBX的慢性全身给药模仿了后面的观察结果。结论集体而言，