The impact of social isolation on HPA axis function, anxiety-like behaviors, and ethanol drinking.
The impact of social isolation on HPA axis function, anxiety-like behaviors, and ethanol drinking.
复制标题
DOI：
10.3389/fnint.2013.00102
复制
发表时间：
2014
影响因子：
3.5
通讯作者：
Weiner JL
中科院分区：
文献类型：
--
作者：
Butler TR;Ariwodola OJ;Weiner JL
下丘脑 - 垂体 - 肾上腺（HPA）轴的失调常见于酗酒者、遭受早期生活应激的人类以及乙醇（EtOH）依赖的动物模型中。我们在一个早期生活应激的啮齿动物模型中检测了HPA轴的功能，该模型会导致酗酒的行为和神经生物学风险因素增加。青春期期间，长 - 埃文斯雄性大鼠被分组饲养（GH）或社会隔离（SI）6周。我们检测了在有和没有地塞米松（DEX）的情况下对应激的皮质酮（CORT）反应以及焦虑样行为。在DEX抑制试验和行为测定之后，一半的大鼠组在家庭笼、两瓶选择间歇性获取模型中进行了6周的乙醇饮用。一部分大鼠组未接触乙醇，但用于基底外侧杏仁核（BLA）中谷氨酸能突触可塑性的电生理测量。相关性分析检测了CORT测量值、焦虑样行为以及乙醇摄入/偏好之间的关系。经过DEX预处理，SI大鼠在急性应激时未能抑制CORT；GH大鼠则表现出显著的抑制。在SI大鼠中，基线CORT与高架十字迷宫开放臂时间之间存在显著的负相关，并且基线CORT与乙醇摄入和偏好之间都存在显著的正相关。在GH大鼠中未观察到基线CORT与行为测量值之间存在显著关系。GH和SI大鼠之间BLA中的谷氨酸能可塑性在程度上相似，并且不受外源性应用CORT的影响。这些数据表明，HPA轴功能受SI影响，这与先前的焦虑样行为有关，并且可能使未来易于自我摄入乙醇。SI大鼠中HPA轴功能、焦虑和乙醇测量值之间的关系进一步加强了该范式在模拟情感障碍和酗酒易感性方面的实用性。
Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is often observed in alcoholics and humans subjected to early life stress, and animal models of ethanol (EtOH) dependence. We examined HPA axis function in a rodent model of early life stress that engenders increases in behavioral and neurobiological risk factors of alcoholism. Long-Evans male rats were group housed (GH) or socially isolated (SI) for 6 weeks during adolescence. We examined the corticosterone (CORT) response to stress with and without dexamethasone (DEX) and anxiety-like behaviors. Following the DEX suppression test and behavioral assays, half of the cohort engaged in 6 weeks of EtOH drinking in a homecage, two-bottle choice intermittent access model. A subset of the cohort was not exposed to EtOH, but was used for electrophysiological measurement of glutamatergic synaptic plasticity in the basolateral amygdala (BLA). Correlational analyses examined relationships between measures of CORT, anxiety-like behaviors, and EtOH intake/preference. With DEX pre-treatment, SI rats failed to suppress CORT in response to an acute stress; GH rats showed a significant suppression. In SI rats, there was a significant negative correlation between baseline CORT and elevated plus maze open arm time, as well as significant positive correlations between baseline CORT and both EtOH intake and preference. No significant relationships between baseline CORT and behavioral measures were observed in GH rats. Glutamatergic plasticity in the BLA was similar in magnitude between GH and SI rats, and was not altered by exogenous application of CORT. These data suggest that HPA axis function is affected by SI, and this is related to antecedent anxiety-like behavior and may predispose for future EtOH self-administration. Relationships between HPA axis function, anxiety, and EtOH measures in SI rats further strengthens the utility of this paradigm in modeling vulnerability for affective disorders and alcoholism.