Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats
Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats
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DOI：
10.1038/s41467-019-09183-0
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发表时间：
2019-03-18
影响因子：
16.6
通讯作者：
George, Olivier
中科院分区：
文献类型：
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作者：
de Guglielmo, Giordano;Kallupi, Marsida;George, Olivier
在酒精戒断过程中，杏仁核中央核(CEA)中的神经元团被激活，这被认为是导致依赖大鼠高水平饮酒的原因。在本研究中，我们描述了通过慢性酒精暴露而激活的CEA神经元集合含有类似于80%的促肾上腺皮质激素释放因子(CRF)神经元，这些CEA CRF+神经元的光遗传失活阻止了神经元集合的招募，减少了饮酒的升级，并降低了躯体戒断迹象的强度。对下游神经元通路的光遗传学分析表明，在抑制CEA、CRF向终纹床核(BNST)的投射后，可以观察到成瘾行为的逆转，CRFCeA-BNST通路的抑制是通过抑制CRF-CRF1系统和抑制BNST细胞的放电而实现的。这些结果表明，CRFCeA-BNST通路可以作为治疗酒精使用障碍中过度饮酒的靶点。
The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains similar to 80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRFCeA-BNST pathway is mediated by inhibition of the CRF-CRF1 system and inhibition of BNST cell firing. These results suggest that the CRFCeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.