催产素
有条件地点偏好
催产素受体
环境富集
酒
背景(考古学)
前额叶皮质
心理学
乙醇
神经肽
敌手
内分泌学
内科学
受体
化学
神经科学
医学
生物
生物化学
认知
古生物学
作者
Mariana Rae,Panos Zanos,Polymnia Georgiou,Priti Chivers,Alexis Bailey,Rosana Camarini
标识
DOI:10.1016/j.neuropharm.2018.06.013
摘要
Environmental conditions, such as stress and environmental enrichment (EE), influence predisposition to alcohol use/abuse; however, the underlying mechanisms remain unknown. To assess the effect of environmental conditions on the initial rewarding effects of alcohol, we examined conditioned place-preference (CPP) to alcohol following exposure to EE in mice. Since social context is a major factor contributing to initial alcohol-drinking, we also assessed the impact of EE on the levels of the "social neuropeptide" oxytocin (OT) and its receptor, OTR. Finally, we assessed the effect of pharmacological manipulations of the oxytocinergic system on EE-induced alcohol CPP. While EE increased sociability and reduced anxiety-like behaviors, it caused a ∼3.5-fold increase in alcohol reward compared to controls. EE triggered profound neuroadaptations of the oxytocinergic system; it increased hypothalamic OT levels and decreased OTR binding in the prefrontal cortex and olfactory nuclei of the brain. Repeated administration of the OT analogue carbetocin (6.4 mg/kg/day) mimicked the behavioral effects of EE on ethanol CPP and induced similar brain region-specific alterations of OTR binding as those observed following EE. Conversely, repeated administration of the OTR antagonist L,369-899 (5 mg/kg/day) during EE exposure, but not during the acquisition of alcohol CPP, reversed the pronounced EE-induced ethanol rewarding effect. These results demonstrate for the first time, a stimulatory effect of environmental enrichment exposure on alcohol reward via an oxytocinergic-dependent mechanism, which may predispose to alcohol abuse. This study offers a unique prospective on the neurobiological understanding of the initial stages of alcohol use/misuse driven by complex environmental-social interplay.
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