Basal and isoproterenol-stimulated cyclic-adenosine monophosphate levels in mouse hippocampus and lymphocytes during alcohol tolerance and withdrawal

Abstract

Aims: 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. Methods: 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. Results: 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the magnitude of isoproterenol-induced net increase was significantly lower in the tolerant, and higher in the ethanol-withdrawn, animals. Conclusions: 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.