Receptor and membrane function in the alcohol tolerant/dependent animal.

ABSTRACT

Neurochemical changes which are associated with the development or expression of tolerance to or physical dependence on ethanol may be expected to display a time course of appearance and disappearance which correlates positively with the time course for tolerance or dependence. Previous studies of striatal dopaminergic receptor function indicated that ethanol-withdrawn mice displayed decreased physiological and biochemical responses to dopamine (DA) agonists, which could be best explained by postulating an inefficient coupling between DA receptors and various receptor-mediated processes, possibly as a result of ethanol-induced changes in neuronal membrane properties. The membrane-bound enzyme, (Na+-K+)ATPase, obtained from ethanol-withdrawn animals, displays an altered transition temperature and resistance to the effects of ethanol on enzyme activity. These changes also suggest compensatory alterations in neuronal membrane properties. All of these alterations show a time course of disappearance which corresponds to that for the disappearance of tolerance to the hypothermic and sedative effects of ethanol. Ethanol-withdrawn mice also display increased numbers of hippocampal muscarinic cholinergic receptors; however, the time course for the increase in receptor number appears to correlate with that of withdrawal symptomatology. Thus, compensatory changes in neuronal membrane properties in response to ethanol may be expressed via diverse functional changes.