Daoust M, Legrand E, Gewiss M, Heidbreder C, DeWitte P, Tran G, Durbin P
Pharmacochimie, U.F.R. Médecine et Pharmacie de Rouen, St. Etienne Du Rouvray, France.
Pharmacol Biochem Behav. 1992 Apr;41(4):669-74. doi: 10.1016/0091-3057(92)90210-7.
Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.
雄性斯普拉格-道利大鼠进行了为期30天的肺部酒精处理。其中6只在酒精处理期间接受阿坎酸（400毫克/千克/天，口服）治疗。对照非酒精处理组在30天内也接受阿坎酸（400毫克/千克/天，口服）治疗。实验结束时，解剖大脑区域（皮质、海马体、丘脑、纹状体和嗅球）用于研究突触体3H-γ-氨基丁酸（GABA）摄取。在另一个实验中，使用高效液相色谱电化学检测法测定相同区域的GABA水平。在酒精处理期间也测量了血液乙醇水平。阿坎酸治疗未改变血液乙醇水平。在皮质和嗅球中，酒精处理增加了3H-GABA摄取（最大速度），亲和力（米氏常数）也增加。在其他脑区，酒精处理未影响3H-GABA摄取。在海马体和丘脑中，阿坎酸治疗仅在酒精处理的大鼠中增强了3H-GABA摄取（最大速度）。此外，在丘脑中，酒精处理提高了GABA水平。讨论了酒精和阿坎酸对GABA突触前事件的影响，并得出结论，乙醇和阿坎酸对GABA转运的作用可能部分负责阿坎酸治疗对乙醇行为的调节。
