Smith Karen L, John Catherine S, Sypek Elizabeth I, Ongür Dost, Cohen Bruce M, Barry Sarah M, Bechtholt Anita J
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts; Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts.
Alcohol Clin Exp Res. 2014 May;38(5):1307-14. doi: 10.1111/acer.12361. Epub 2014 Mar 21.
Alcoholism is associated with specific brain abnormalities revealed through postmortem studies, including a reduction in glial cell number and dysregulated glutamatergic neurotransmission. Whether these abnormalities contribute to the etiology of alcoholism, are consequences of alcohol use, or both is still unknown.
We investigated the role of astrocytic glutamate uptake in ethanol (EtOH) binge drinking in mice, using the "drinking in the dark" (DID) paradigm by blocking the astrocytic glutamate transporter (GLT-1) with intracerebroventricular (ICV) administration of dihydrokainic acid (DHK). To determine whether astrocytic glutamate uptake regulates the conditioned rewarding effects of EtOH, we examined the effects of ICV DHK on the acquisition and expression of EtOH-induced conditioned place preference.
Blocking central astrocytic glutamate uptake selectively attenuated EtOH binge drinking behavior in mice. DHK did not alter the acquisition or expression of preference for EtOH-associated cues, indicating that reduced astrocytic glutamate trafficking may decrease binge-like drinking without altering the conditioned rewarding effects of EtOH.
Several alternative conclusions are plausible, however, interpreting these data in the context of the human literature, these findings suggest that the reduction of glia in the alcoholic brain may not be a predisposing factor to developing alcoholism and could be a consequence of EtOH toxicity that decreases excessive EtOH intake.
通过尸检研究发现，酒精中毒与特定的脑异常有关，包括神经胶质细胞数量减少和谷氨酸能神经传递失调。这些异常是导致酒精中毒的病因、饮酒的后果，还是两者兼而有之，目前仍不清楚。
我们通过脑室内注射二氢卡因酸（DHK）阻断星形胶质细胞谷氨酸转运体（GLT-1），利用“黑暗中饮酒”（DID）范式研究星形胶质细胞谷氨酸摄取在小鼠乙醇（EtOH）暴饮中的作用。为了确定星形胶质细胞谷氨酸摄取是否调节EtOH的条件性奖赏效应，我们研究了脑室内注射DHK对EtOH诱导的条件性位置偏爱获取和表达的影响。
阻断中枢星形胶质细胞谷氨酸摄取可选择性减弱小鼠的EtOH暴饮行为。DHK并未改变对EtOH相关线索的偏爱获取或表达，这表明星形胶质细胞谷氨酸转运减少可能会减少暴饮样饮酒行为，而不会改变EtOH的条件性奖赏效应。
然而，有几个替代结论是合理的。结合人类文献来解释这些数据，这些发现表明，酒精性脑病中神经胶质细胞减少可能不是酒精中毒的易感因素，可能是EtOH毒性导致过量EtOH摄入减少的结果。
