UNASSIGNED: In the present report we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice.
UNASSIGNED: Using chemogenetic tools we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male, but not female, mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF type-1 receptor (CRF1R) in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF2R activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking blunted CRF mRNA in the CeA regardless of sex.
UNASSIGNED: These observations provide novel evidence that CRF+ CeA to LH neurocircuitry modulates binge-like ethanol intake in male, but not female mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.
■在本报告中,我们表征了杏仁核中央核(CeA)和支配下丘脑外侧(LH)的CRF神经回路,以调节雄性和雌性小鼠的暴饮暴食样乙醇摄入量。
■使用化学遗传学工具,我们发现沉默CRFCeA至LH回路显着减弱了男性的狂欢样乙醇摄入量,但不是女性,mouse.始终如一,CeA神经元中CRF的遗传缺失仅抑制了雄性小鼠的乙醇摄入量。此外,LH中CRF1型受体(CRF1R)的药理学阻断仅在雄性小鼠中显着降低了暴饮暴食样乙醇的摄入量,而LH中的CRF2R激活未能改变两种性别的乙醇摄入量。最后,暴饮暴食样乙醇的历史使CeA中的CRFmRNA变得迟钝,无论性别。
■这些观察结果提供了新的证据,表明CRF+CeA到LH神经回路调节男性暴饮暴食样乙醇的摄入量,但不是雌性老鼠,这可能有助于深入了解指导暴饮暴食样乙醇摄入量中已知性别差异的机制。