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

Abstract

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the magnitude of isoproterenol-induced net increase was significantly lower in the tolerant, and higher in the ethanol-withdrawn, animals.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