Alcohol and Alcoholism Vol. 38, No. 1, pp. 11-17, 2003
© 2003 Medical Council on Alcohol
BASAL AND ISOPROTERENOL-STIMULATED CYCLIC-ADENOSINE MONOPHOSPHATE LEVELS IN MOUSE HIPPOCAMPUS AND LYMPHOCYTES DURING ALCOHOL TOLERANCE AND WITHDRAWAL
1 Institute of Diagnostics and Management, University of Pécs and
2 Central Laboratory, Markusovszky Teaching Hospital, H-9700 Szombathely, Markusovszky St. 3, Hungary
Received 20 February 2002; first review notified 28 June 2002; accepted 8 July 2002
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the magnitude of isoproterenol-induced net increase was significantly lower in the tolerant, and higher in the ethanol-withdrawn, animals.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.