Dar M S, Mustafa S J, Wooles W R
Life Sci. 1983 Oct 3;33(14):1363-74. doi: 10.1016/0024-3205(83)90819-6.
The ability of adenosine to modify the CNS effects of acute and chronic ethanol was studied by using theophylline, an adenosine antagonist, and dipyridamole, a blocker of adenosine reuptake. We also studied the binding characteristics of adenosine using crude membranes of whole brain. Theophylline pretreatment prior to acute ethanol administration markedly reduced the duration of ethanol-induced sleep and similarly decreased the intensity and duration of motor incoordination. In chronic ethanol treated mice the effect of theophylline on ethanol-induced hypnosis and motor incoordination was similar to the acute experiment. Dipyridamole markedly prolonged the duration of ethanol-induced hypnosis and potentiated the motor incoordination produced by acute ethanol. However, in chronic ethanol treated mice dipyridamole was not able to potentiate the motor incoordinating effect of ethanol although it was able to prolong ethanol hypnosis similar to the results obtained in the acute ethanol study. Neither drug had any effect on ethanol-induced hypothermia, in either the acute or chronic studies. After 10 days of ethanol ingestion the adenosine dissociation constant was unchanged whereas the number of brain adenosine receptors was increased 28% although the increase did not reach statistical significance. The number of adenosine receptors was reduced 40% at 24 and 48 h after withdrawal and returned to prewithdrawal levels at 72 h. The dissociation constant was reduced at 24 and 48 h but by 72 h had returned to prewithdrawal levels. The marked changes in adenosine binding characteristics as well as the modification of some CNS effects of ethanol by drugs which influence either adenosine binding to its receptor or the availability of adenosine suggests that adenosine may be involved in the expression of some of the CNS effects of ethanol.
通过使用腺苷拮抗剂茶碱和腺苷再摄取阻滞剂双嘧达莫，研究了腺苷对急性和慢性乙醇中枢神经系统效应的影响。我们还使用全脑粗膜研究了腺苷的结合特性。急性乙醇给药前用茶碱预处理可显著缩短乙醇诱导的睡眠时间，并同样降低运动不协调的强度和持续时间。在慢性乙醇处理的小鼠中，茶碱对乙醇诱导的催眠和运动不协调的影响与急性实验相似。双嘧达莫显著延长了乙醇诱导的催眠时间，并增强了急性乙醇产生的运动不协调。然而，在慢性乙醇处理的小鼠中，双嘧达莫虽然能够延长乙醇诱导的催眠时间，与急性乙醇研究结果相似，但却不能增强乙醇的运动不协调作用。在急性和慢性研究中，这两种药物对乙醇诱导的体温过低均无任何影响。乙醇摄入10天后，腺苷解离常数未变，而脑腺苷受体数量增加了28%，尽管增加未达到统计学显著水平。戒断后24小时和48小时，腺苷受体数量减少了40%，72小时时恢复到戒断前水平。解离常数在24小时和48小时时降低，但到72小时时已恢复到戒断前水平。腺苷结合特性的显著变化以及影响腺苷与其受体结合或腺苷可用性的药物对乙醇某些中枢神经系统效应的改变表明，腺苷可能参与了乙醇某些中枢神经系统效应的表达。
