Volicer L, Hurter B P
J Pharmacol Exp Ther. 1977 Feb;200(2):298-305.
The effect of ethanol on cyclic nucleotide levels was investigated in male Sprague-Dawley rats. The rats were sacrificed by microwave irradiation, the brains were divided into four areas, and cyclic nucleotides were measured by radioimmunoassays. Administration of a single dose of ethanol per os produced a dose-dependent decrease of adenosine 3':5'-monophosphate (cyclic AMP) in cerebral cortex, cerebellum, pons and medulla oblongata while guanosine 3':5'-monophosphate (cyclic GMP) was decreased in all brain areas. Dependence on ethanol was induced by three daily administrations of ethanol p.o. for 7 days. The last dose of ethanol did not produce any decrease of cyclic AMP levels while the decrease of cyclic GMP levels was still present. During ethanol withdrawal cyclic AMP levels increased in cerebral cortex, pons and medulla oblongata and did not change in cerebellum. Changes of cyclic AMP in subcortex were more complex. Cyclic GMP levels increased during ethanol withdrawal in cerebellum, pons and medulla oblongata and did not change in cerebral cortex and subcortex. These results indicate that changes of cyclic nucleotides might participate in the mechanism of ethanol dependence and withdrawal.
研究了乙醇对雄性斯普拉格-道利大鼠环核苷酸水平的影响。通过微波辐射处死大鼠，将大脑分为四个区域，并用放射免疫分析法测定环核苷酸。经口给予单剂量乙醇会使大脑皮层、小脑、脑桥和延髓中的3':5'-单磷酸腺苷（环磷酸腺苷，cyclic AMP）呈剂量依赖性降低，而所有脑区中的3':5'-单磷酸鸟苷（环磷酸鸟苷，cyclic GMP）均降低。通过连续7天每日经口给予乙醇诱导大鼠对乙醇产生依赖性。最后一剂乙醇并未使环磷酸腺苷水平降低，而环磷酸鸟苷水平仍降低。在乙醇戒断期间，大脑皮层、脑桥和延髓中的环磷酸腺苷水平升高，小脑则无变化。皮层下区域的环磷酸腺苷变化更为复杂。在乙醇戒断期间，小脑、脑桥和延髓中的环磷酸鸟苷水平升高，大脑皮层和皮层下区域则无变化。这些结果表明，环核苷酸的变化可能参与了乙醇依赖和戒断的机制。
