Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.
Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.
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DOI：
10.1038/nature11436
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发表时间：
2012-10-18
期刊：
影响因子：
64.8
通讯作者：
Phillips, Paul E. M.
中科院分区：
文献类型：
--
作者：
Lemos, Julia C.;Wanat, Matthew J.;Smith, Jeffrey S.;Reyes, Beverly A. S.;Hollon, Nick G.;Van Bockstaele, Elisabeth J.;Chavkin, Charles;Phillips, Paul E. M.
压力源激发了一系列的适应性反应，从“战斗或逃跑”到促进长期目标的内部紧迫信号。然而，创伤性或慢性不可控制的压力促进了重度抑郁症的发作，其中急性压力源失去了其动力特性，并被视为不可逾越的障碍。因此，压力引起的抑郁症是一种使人衰弱的疾病，其特征是情感从环境的参与转变为退缩。抑郁症和相关病理学的一个新兴的神经生物学基底是丘脑核，这是一个能够通过连接边缘系统、认知和运动回路来介导各种压力反应的区域。在这里，我们报告，促肾上腺皮质激素释放因子（CRF），神经肽释放急性应激和其他引起环境刺激，在幼稚小鼠的丘脑核的行动，增加多巴胺的释放，通过共激活的CRF R1和R2受体。值得注意的是，严重的压力暴露完全消除了这种影响，至少90天没有恢复。CRF调节丘脑核多巴胺释放能力的丧失伴随着对CRF的反应从食欲转变为厌恶，表明对急性应激源的情绪反应发生了根本性的变化。因此，目前的研究结果提供了一个生物基板开关的影响，这是中央压力引起的抑郁症。
Stressors motivate an array of adaptive responses ranging from “fight or flight” to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of Major Depressive Disorder where acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naïve mice to increase dopamine release through co-activation of CRF R1 and R2 receptors. Remarkably, severe stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF’s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.
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DOI：
10.1007/bf02284835
发表时间：
1996-12-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Peters, A;Palay, SL
通讯作者：
Palay, SL
影响因子：
2.5
作者：
FINK, JS;SMITH, GP
通讯作者：
SMITH, GP
影响因子：
3.4
作者：
Bruchas, Michael R.;Chavkin, Charles
通讯作者：
Chavkin, Charles
影响因子：
2.9
作者：
CADOR, M;AHMED, SH;STINUS, L
通讯作者：
STINUS, L
影响因子：
8.2
作者：
Korte, SM;Koolhaas, JM;McEwen, BS
通讯作者：
McEwen, BS