Alteration in cerebral GABAB receptor functions during formation of alcohol dependence.

Alterations in the function of cerebral GABAB receptor systems were studied in alcohol dependent animals and reconstituted GABAB receptor systems in vitro. The GABAB receptor binding at both high and low affinity sites showed a significant increase during the formation of alcohol dependence and alcohol withdrawal, although ethanol at a low concentration did not affect the GABAB receptor binding in vitro. On the other hand, a low concentration (100 mM) of ethanol, which had no significant effect on GABAB receptor binding, inhibited cAMP accumulation in vitro. The cAMP formation in brain did not show significant changes during the formation of alcohol dependence in spite of the increase in GABAB receptor binding. These results indicate that alcohol dependence induces an increase of GABAB receptor binding in the brain. This increase in GABAB receptor binding, however, may not be associated with the changes in the GABAB receptor mediated suppression of cAMP formation, possibly due to the deterioration of the coupling between the GABAB receptor and the Gi/Go type of GTP binding protein/adenylyl cyclase. Furthermore, the present results suggest that in vitro addition of ethanol may have differential effects on cerebral GABAB receptor systems as compared with those found in the brain of alcohol dependent subjects.