Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
Neuropsychopharmacology. 2014 Feb;39(3):579-94. doi: 10.1038/npp.2013.230. Epub 2013 Sep 2.
Repeated cycles of binge alcohol drinking and abstinence are key components in the development of dependence. However, the precise behavioral mechanisms underlying binge-like drinking and its consequences on striatal synaptic physiology remain unclear. In the present study, ethanol and water drinking patterns were recorded with high temporal resolution over 6 weeks of binge-like ethanol drinking using the 'drinking in the dark' (DID) protocol. The bottle exchange occurring at the beginning of each session prompted a transient increase in the drinking rate that might facilitate the acquisition of ethanol binge-like drinking. Ethanol drinking mice also displayed a 'front-loading' behavior, in which the highest rate of drinking was recorded during the first 15 min. This rate increased over weeks and paralleled the mild escalation of blood ethanol concentrations. GABAergic and glutamatergic transmission in the dorsal striatum were examined following DID. Spontaneous glutamatergic transmission and the density of dendritic spines were unchanged after ethanol drinking. However, the frequency of GABAA receptor-mediated inhibitory postsynaptic currents was depressed in medium spiny neurons of ethanol drinking mice. A history of ethanol drinking also increased ethanol preference and altered the acute ethanol effects on GABAergic transmission differentially in dorsolateral and dorsomedial striatum. Together, the study shows that the bottle exchange during DID promotes fast, voluntary ethanol drinking and that this intermittent pattern of ethanol drinking causes a depression of GABAergic transmission in the dorsal striatum.
反复的 binge 饮酒和戒断循环是依赖形成的关键因素。然而， binge 样饮酒及其对纹状体突触生理学影响的确切行为机制仍不清楚。在本研究中，我们使用“暗室饮酒”（DID）方案，在 6 周 binge 样乙醇饮酒期间，以高时间分辨率记录乙醇和水的饮酒模式。在每次 session 开始时的瓶交换会促使饮酒率短暂增加，这可能有助于乙醇 binge 样饮酒的获得。乙醇饮酒小鼠还表现出“前置加载”行为，即在最初的 15 分钟内记录到最高的饮酒率。该速率在数周内增加，与血液乙醇浓度的轻度升高平行。在 DID 之后，检查了背侧纹状体中的 GABA 能和谷氨酸能传递。乙醇饮酒后，自发性谷氨酸能传递和树突棘密度没有变化。然而，乙醇饮酒小鼠的中脑神经元中 GABAA 受体介导的抑制性突触后电流的频率降低。乙醇饮酒的历史还增加了对乙醇的偏好，并在背外侧和背内侧纹状体中以不同的方式改变了急性乙醇对 GABA 能传递的影响。总之，该研究表明 DID 期间的瓶交换促进了快速、自愿的乙醇饮酒，而这种间歇性的乙醇饮酒模式导致背侧纹状体中 GABA 能传递的抑制。
