Piepponen T Petteri, Kiianmaa Kalervo, Ahtee Liisa
Department of Pharmacy, Division of Pharmacology and Toxicology, University of Helsinki, P.O. Box 56, FIN-00014, Helsinki, Finland.
Pharmacol Biochem Behav. 2002 Dec;74(1):21-30. doi: 10.1016/s0091-3057(02)00937-1.
Effects of ethanol on the accumbal extracellular concentrations of dopamine, as well as of the amino acid transmitters gamma-amino butyric acid (GABA), glutamate and taurine, were studied in the alcohol-insensitive (alcohol-tolerant, AT) and alcohol-sensitive (alcohol-nontolerant, ANT) rats selected for low and high sensitivity to ethanol-induced motor impairment. Ethanol (2 or 3 g/kg ip) enhanced the output of dopamine and its metabolites in freely moving rats of both lines as measured by in vivo microdialysis. The effect of ethanol on the metabolites of dopamine tended to be stronger in the ANT rats. The smaller dose of ethanol decreased the output of GABA only in the AT rats, whereas the larger dose of ethanol decreased the output of GABA in rats of both lines to a similar degree. Ethanol at the dose of 2 g/kg slightly, but statistically, significantly decreased the output of glutamate in rats of both lines, but the larger dose of ethanol decreased the output of glutamate only in the AT rats. Ethanol at the dose of 2 g/kg induced a small transient increase in the output of taurine within 2 h after its administration in rats of both lines, but the larger dose of ethanol was without significant effect. These results confirm the previous findings that ethanol suppresses the release of GABA more in the AT than ANT rats. Thus, among the neurotransmitter systems we studied, the effects of ethanol might be the most relevant on GABAergic transmission regarding the sensitivity towards ethanol. However, our findings suggest that glutamate is also involved in this respect.
在对乙醇诱导的运动障碍低敏感性(耐酒精,AT)和高敏感性(不耐酒精,ANT)的大鼠中,研究了乙醇对伏隔核细胞外多巴胺以及氨基酸递质γ-氨基丁酸(GABA)、谷氨酸和牛磺酸浓度的影响。通过体内微透析测量,乙醇(2或3 g/kg腹腔注射)增强了两品系自由活动大鼠中多巴胺及其代谢产物的释放。乙醇对多巴胺代谢产物的影响在ANT大鼠中往往更强。较小剂量的乙醇仅降低了AT大鼠中GABA的释放,而较大剂量的乙醇使两品系大鼠中GABA的释放降低到相似程度。2 g/kg剂量的乙醇轻微但在统计学上显著降低了两品系大鼠中谷氨酸的释放,但较大剂量的乙醇仅降低了AT大鼠中谷氨酸的释放。2 g/kg剂量的乙醇在给药后2小时内使两品系大鼠中牛磺酸的释放出现短暂小幅增加,但较大剂量的乙醇无显著影响。这些结果证实了先前的发现,即乙醇对GABA释放的抑制在AT大鼠中比ANT大鼠中更强。因此,在我们研究的神经递质系统中,就对乙醇的敏感性而言,乙醇的作用可能与GABA能传递最为相关。然而,我们的研究结果表明谷氨酸在这方面也有参与。