The Changing View of Ethanol’s Actions: From Generalities to Specifics
The development of an addiction on ethanol involves a number of phenomena arising from the actions of ethanol on the central nervous system (CNS). These phenomena include ethanol-induced intoxication, reinforcement, the development of functional tolerance and physical dependence and ethanol-induced brain damage. One of the more popular hypotheses regarding the cellular and molecular mechanisms by which ethanol produces its effect on the CNS proposes that ethanol acts by disordering (fluidizing) the lipids of neuronal membranes (Meyer and Gottlieb, 1926; Chin and Goldstein, 1977). The disorder of the structural matrix of the neuronal membrane is thought to secondarily affect the activity of the functional proteins (receptors, ionophores, enzymes) residing in this (lipid) matrix. The “lipid hypothesis” of ethanol’s actions has recently been challenged, however, because relatively high concentrations of ethanol are necessary to produce lipid perturbations of the magnitude produced by even normal variations in body temperature (Tabakoff, Hoffman, and MacLaughlin, 1988). In addition, recent research has provided evidence of a selectivity of ethanol’s effects on various neuronal membrane proteins which cannot be explained simply by invoking an ethanol-induced perturbation of membrane lipid structure. Some of the most ethanol sensitive membrane proteins are the receptor-gated ion channels. The burgeoning knowledge of the physiologic roles of these channels and the responses of these proteins to the acute and chronic effects of ethanol suggests that particular systems may play a major role in the expression of the various physiologic and behavioral effects of ethanol. This overview will attempt to summarize the evidence that certain receptor-gated ion channels may be considered as specific “receptive systems” for ethanol in the CNS. We will also provide evidence on how certain neurohormones can modify the actions of ethanol within the CNS.
KeywordsNMDA Receptor Arginine Vasopressin Fetal Alcohol Syndrome Ethanol Tolerance Ethanol Withdrawal
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