Kovács Gábor L, Toldy Erzsébet
Institute of Diagnostics and Management, University of Pécs, Hungary.
Alcohol Alcohol. 2003 Jan-Feb;38(1):11-7. doi: 10.1093/alcalc/agg018.
Basal and isoproterenol-stimulated levels of cyclic-adenosine monophosphate (cAMP) were investigated in the brain (hippocampus) and in the lymphocytes of mice rendered tolerant to, and physically dependent on, ethanol.
cAMP was measured with radioimmunoassay. Tolerance to, and physical dependence on, ethanol were induced by a 14-day ingestion of ethanol in drinking water. Upon replacing ethanol with water, ethanol withdrawal was precipitated and measured by the intensity of withdrawal-induced hyperexcitability and seizures.
Basal (non-stimulated) levels of cAMP - both in the hippocampus and in the lymphocytes - were significantly reduced in the alcohol-drinking tolerant and physically dependent animals, but significantly increased 24 h after the onset of withdrawal. Isoproterenol resulted in a dose-dependent stimulation of cAMP in all groups investigated (control, tolerant/physically dependent, withdrawal), however, the magnitude of isoproterenol-induced net increase was significantly lower in the tolerant, and higher in the ethanol-withdrawn, animals.
The major finding of the present experiments is that there was a significant positive correlation between basal cAMP levels in brain and lymphocytes versus the intensity of withdrawal hyperexcitability in ethanol-addicted mice.
研究对乙醇产生耐受且身体依赖的小鼠的脑（海马体）和淋巴细胞中基础及异丙肾上腺素刺激的环磷酸腺苷（cAMP）水平。
采用放射免疫分析法测定cAMP。通过在饮水中摄入乙醇14天诱导小鼠对乙醇产生耐受和身体依赖。用纯水替代乙醇后，引发乙醇戒断反应，并通过戒断诱导的过度兴奋和癫痫发作的强度来衡量。
在对乙醇产生耐受且身体依赖的动物中，海马体和淋巴细胞中的基础（未刺激）cAMP水平显著降低，但在戒断开始24小时后显著升高。异丙肾上腺素在所有研究组（对照组、耐受/身体依赖组、戒断组）中均导致cAMP呈剂量依赖性刺激，然而，异丙肾上腺素诱导的净增加幅度在耐受动物中显著较低，在乙醇戒断动物中较高。
本实验的主要发现是，在乙醇成瘾小鼠中，脑和淋巴细胞中的基础cAMP水平与戒断过度兴奋强度之间存在显著正相关。
