Steger Jennifer S, Land Benjamin B, Lemos Julia C, Chavkin Charles, Phillips Paul E M
Center of Excellence in Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, United States.
Department of Pharmacology, University of Washington, Seattle, WA, United States.
Front Behav Neurosci. 2020 Oct 5;14:564054. doi: 10.3389/fnbeh.2020.564054. eCollection 2020.
Stress is highly pervasive in humans, impacting motivated behaviors with an enormous toll on life quality. Many of the effects of stress are orchestrated by neuropeptides such as corticotropin-releasing factor (CRF). It has previously been shown that in stress-naïve male mice, CRF acts in the core of the nucleus accumbens (NAc) to produce appetitive effects and to increase dopamine release; yet in stress-exposed male mice, CRF loses its capacity to modulate NAc dopamine release and is aversive. In the current research, we tested whether this effect is comparable in females to males and whether the neuroadaptation is susceptible to social transmission. We found that, like in males, CRF increased dopamine release in stress-naïve but not stress-exposed female mice. Importantly, this persistent physiological change was not accompanied by overt behavioral changes that would be indicative of depression- or anxiety-like phenotype. Nonetheless, when these mice were housed for 7 days with stress-naïve conspecifics, the cage mates also exhibited a loss of dopamine potentiation by CRF. These data demonstrate the asymptomatic, yet pervasive transmission of stress-related neuroadaptations in the population.
压力在人类中极为普遍,影响着动机行为,对生活质量造成巨大损害。压力的许多影响是由神经肽如促肾上腺皮质激素释放因子(CRF)所调控的。此前已有研究表明,在未经历过压力的雄性小鼠中,CRF作用于伏隔核(NAc)核心区域,产生奖赏效应并增加多巴胺释放;然而,在经历过压力的雄性小鼠中,CRF失去了调节NAc多巴胺释放的能力,且产生厌恶效应。在当前研究中,我们测试了这种效应在雌性小鼠中是否与雄性小鼠相当,以及这种神经适应性是否易于发生社会传递。我们发现,与雄性小鼠一样,CRF在未经历过压力的雌性小鼠中增加多巴胺释放,但在经历过压力的雌性小鼠中则不然。重要的是,这种持续的生理变化并未伴随着表明抑郁或焦虑样表型的明显行为变化。尽管如此,当这些小鼠与未经历过压力的同种小鼠共同饲养7天时,笼中的同伴也表现出CRF诱导的多巴胺增强作用丧失。这些数据证明了压力相关神经适应性在群体中无症状但普遍存在的传递。