Alcohol abuse is a worldwide public health concern, yet the precise molecular targets of alcohol in the brain are still not fully understood. Alcohol may promote its euphoric and motivational effects, in part, by activating the endogenous opioid system. One particular component of this system consists of pro-opiomelanocortin (POMC) producing neurons in the arcuate nucleus (ArcN) of the hypothalamus, which project to reward-related brain areas. To identify the physiological effects of ethanol on ArcN POMC neurons, we utilized whole cell patch-clamp recordings and bath application of ethanol (5-40 mM) to identify alterations in spontaneous baseline activity, rheobase, spiking characteristics or intrinsic neuronal properties. We found that 10mM ethanol increased the number of depolarization-induced spikes in the majority of recorded cells, whereas higher concentrations of ethanol (20-40mM) decreased the number of spikes. Interestingly, we found that basal firing rates of ArcN POMC neurons may predict physiological responding to ethanol. Rheobase and spontaneous activity, measured by spontaneous excitatory post-synaptic potentials (EPSPs) at rest, were unchanged after exposure to ethanol, regardless of concentration. These results suggest that ethanol has concentration-dependent modulatory effects on ArcN POMC neuronal activity, which may be relevant to treatments for alcohol use disorders that target endogenous opioid systems.

中文翻译：

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乙醇对下丘脑 POMC 神经元兴奋性具有浓度依赖性影响。

酗酒是一个全球性的公共卫生问题，但大脑中酒精的精确分子靶点仍未完全了解。酒精可能会促进其欣快感和激励作用，部分原因是通过激活内源性阿片类药物系统。该系统的一个特殊组成部分是下丘脑弓状核 (ArcN) 中产生阿黑皮素原 (POMC) 的神经元，这些神经元投射到与奖赏相关的大脑区域。为了确定乙醇对 ArcN POMC 神经元的生理影响，我们利用全细胞膜片钳记录和乙醇 (5-40 mM) 浴应用来确定自发基线活动、rheobase、尖峰特征或内在神经元特性的变化。我们发现 10 mM 乙醇增加了大多数记录细胞中去极化诱导的尖峰数量，而更高浓度的乙醇 (20-40 mM) 会减少尖峰的数量。有趣的是，我们发现 ArcN POMC 神经元的基础放电率可以预测对乙醇的生理反应。Rheobase 和自发活动，通过自发兴奋性突触后电位 (EPSPs) 在休息时测量，在暴露于乙醇后没有变化，无论浓度如何。这些结果表明，乙醇对 ArcN POMC 神经元活动具有浓度依赖性调节作用，这可能与针对内源性阿片类药物系统的酒精使用障碍的治疗有关。通过静息时自发兴奋性突触后电位 (EPSP) 测量，暴露于乙醇后，无论浓度如何，均未发生变化。这些结果表明，乙醇对 ArcN POMC 神经元活动具有浓度依赖性调节作用，这可能与针对内源性阿片类药物系统的酒精使用障碍的治疗有关。通过静息时自发兴奋性突触后电位 (EPSP) 测量，暴露于乙醇后，无论浓度如何，均未发生变化。这些结果表明，乙醇对 ArcN POMC 神经元活动具有浓度依赖性调节作用，这可能与针对内源性阿片类药物系统的酒精使用障碍的治疗有关。