Disentangling the effects of Corticotrophin Releasing Factor and GABA release from the ventral bed nucleus of the stria terminalis on ethanol self-administration in mice.
Disentangling the effects of Corticotrophin Releasing Factor and GABA release from the ventral bed nucleus of the stria terminalis on ethanol self-administration in mice.
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解开终纹腹侧床核释放促肾上腺皮质激素释放因子和 GABA 对小鼠自我给药乙醇的影响。
DOI：
10.1101/2023.03.02.530838
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
TL,Kash
中科院分区：
文献类型：
--
作者：
CA,Gianessi;GB,Gereau;HL,Haun;D,Pati;T,Sides;SL,D'Ambrosio;K,Boyt;WP,Kelson;CW,Hodge;TL,Kash
过量饮酒会造成极大的伤害和负面的健康后果。促肾上腺皮质激素释放因子(CRF)是一种应激相关神经肽，与酗酒和酒精依赖有关。终纹床核中含有CRF的神经元(BNSTCRF)可以控制酒精的消耗。这些BNSTCRF神经元也释放GABA，这引发了一个问题，控制酒精摄入的是CRF还是GABA释放，还是两者兼而有之。在这里，我们使用病毒载体来分离BNSTCRF神经元释放CRF和GABA对雄性和雌性小鼠在可操作的自我给药范例中酒精摄入量增加的影响。我们发现，BNST神经元中CRF的缺失减少了两性的乙醇摄入量，对男性的影响更大。对于蔗糖自身给药，CRF缺失没有影响。通过敲除vGAT抑制BNSTCRF中GABA的释放，在雄性小鼠中产生了乙醇可操纵性自我给药的一过性增加，并以性别依赖的方式降低了以递增比率强化蔗糖的动力。总而言之，这些结果突显了来自相同神经元群体的不同信号分子如何双向控制行为。此外，他们表明，BNST CRF的释放对于高强度饮酒是重要的，而这些神经元的GABA释放可能在调节动机方面发挥作用。
Excessive alcohol use causes a great deal of harm and negative health outcomes. Corticotrophin releasing factor (CRF), a stress-related neuropeptide, has been implicated in binge ethanol intake and ethanol dependence. CRF containing neurons in the bed nucleus of the stria terminalis (BNSTCRF) can control ethanol consumption. These BNSTCRF neurons also release GABA, raising the question, is it CRF or GABA release or both that is controlling alcohol consumption. Here, we used viral vectors to separate the effects of CRF and GABA release from BNSTCRF neurons on the escalation of ethanol intake in an operant self-administration paradigm in male and female mice. We found that CRF deletion in BNST neurons reduces ethanol intake in both sexes, with a stronger effect in males. For sucrose self-administration there was no effect of CRF deletion. Suppression of GABA release, via knockdown of vGAT, from BNSTCRF produced a transient increase in ethanol operant self-administration following in male mice, and reduced in motivation to work for sucrose on a progressive ratio schedule of reinforcement in a sex-dependent manner. Together, these results highlight how different signaling molecules from the same populations of neurons can bidirectionally control behavior. Moreover, they suggest that BNST CRF release is important for high intensity ethanol drinking that precedes dependence, whereas GABA release from these neurons may play a role in regulating motivation.