Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.
Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.
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DOI：
10.1016/j.neuropharm.2017.02.001
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发表时间：
2017-05-01
影响因子：
4.7
通讯作者：
Mazei-Robison MS
中科院分区：
文献类型：
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作者：
Kaska S;Brunk R;Bali V;Kechner M;Mazei-Robison MS
虽然抑郁症的病因尚未完全清楚，但越来越多的动物模型证据表明腹侧被盖区（VTA）在发病机制中的作用。在本文中，我们研究了VTA雷帕霉素2（TORC 2）信号转导机制的潜在作用，在介导慢性社会失败压力（CSDS），一个完善的抑郁症小鼠模型的易感性。利用Rictor（雷帕霉素靶点的雷帕霉素不敏感伴侣），TORC2的一个必要组成部分的遗传和病毒敲除，我们证明，减少Rictor依赖的TORC2信号在儿茶酚胺能神经元，或特别是在腹侧被盖区，不会改变对CSDS的敏感性。阿片类药物滥用和情绪障碍通常是共病的，以前的数据表明VTA TORC 2在介导阿片类药物奖励中的作用。因此，我们还研究了其在介导CSDS后阿片奖励变化中的潜在作用。在应激未处理小鼠的两瓶选择试验中，Rictor的儿茶酚胺能缺失增加了水、蔗糖和吗啡的摄入量，但没有增加偏好，并且这些效应在应激后保持不变。VTA特异性敲除Rictor增加了CSDS后的水和蔗糖摄入量，但在没有压力的情况下不会改变消费行为。这些研究结果表明，TORC 2在介导压力诱导的完成行为变化中发挥了新的作用，这些变化可能导致情绪障碍的某些方面。
While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS. Opiate abuse and mood disorders are often comorbid, and previous data demonstrate a role for VTA TORC2 in mediating opiate reward. Thus, we also investigated its potential role in mediating changes in opiate reward following CSDS. Catecholaminergic deletion of Rictor increases water, sucrose, and morphine intake but not preference in a two-bottle choice assay in stress-naïve mice, and these effects are maintained after stress. VTA-specific knockout of Rictor increases water and sucrose intake after physical CSDS, but does not alter consummatory behavior in the absence of stress. These findings suggest a novel role for TORC2 in mediating stress-induced changes in consummatory behaviors that may contribute to some aspects of mood disorders.