Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory
Orexin signaling during social defeat stress influences subsequent social interaction behaviour and recognition memory
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DOI：
10.1016/j.bbr.2018.05.032
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发表时间：
2019-01-01
影响因子：
2.7
通讯作者：
Bhatnagar, Seema
中科院分区：
文献类型：
--
作者：
Eacret, Darrell;Grafe, Laura A.;Bhatnagar, Seema
食欲素是在外侧下丘脑中合成的神经肽，其影响唤醒、进食、奖赏途径和对应激的反应。然而，食欲素在反复应激中的作用还没有完全确定。在这里，我们研究了食欲素及其受体如何在反复的社会失败和随后的焦虑和记忆相关行为的应对反应。具体来说，我们使用设计师受体专门激活的设计师药物（DREADDs），以刺激食欲素之前的每一个连续五天的社会失败的压力在成年雄性大鼠。此外，我们通过在每次社交失败之前使用选择性食欲素2受体拮抗剂（MK-1064）来确定食欲素2受体在这些行为中的作用。在5天的社交失败适应期后，在社交互动和新物体识别范式中评价大鼠，以分别评估焦虑样行为和识别记忆。在每次社交失败之前，DREADDs激活食欲素神经元降低了5天内被击败的平均潜伏期，这表明我们先前已经将被动应对策略与压力脆弱表型联系起来。此外，在失败条件反射过程中刺激食欲素信号传导降低了随后的社会互动和新物体识别测试中的表现，表明随后的焦虑样行为增加和识别记忆减少。在反复失败中阻断食欲素2受体并不能改变这些效果。总之，我们的研究结果表明，食欲素神经元激活产生一个被动的应对表型在社会失败，导致随后的焦虑样行为和记忆缺陷。
Orexins are neuropeptides synthesized in the lateral hypothalamus that influence arousal, feeding, reward pathways, and the response to stress. However, the role of orexins in repeated stress is not fully characterized. Here, we examined how orexins and their receptors contribute to the coping response during repeated social defeat and subsequent anxiety-like and memory-related behaviors. Specifically, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to stimulate orexins prior to each of five consecutive days of social defeat stress in adult male rats. Additionally, we determined the role of the orexin 2 receptor in these behaviors by using a selective orexin 2 receptor antagonist (MK-1064) administered prior to each social defeat. Following the 5 day social defeat conditioning period, rats were evaluated in social interaction and novel object recognition paradigms to assess anxiety-like behavior and recognition memory, respectively. Activation of orexin neurons by DREADDs prior to each social defeat decreased the average latency to become defeated across 5 days, indicative of a passive coping strategy that we have previously linked to a stress vulnerable phenotype. Moreover, stimulation of orexin signaling during defeat conditioning decreased subsequent social interaction and performance in the novel object recognition test indicating increased subsequent anxiety-like behavior and reduced recognition memory. Blocking the orexin 2 receptor during repeated defeat did not alter these effects. Together, our results suggest that orexin neuron activation produces a passive coping phenotype during social defeat leading to subsequent anxiety-like behaviors and memory deficits.