Lipid vs protein theories of alcohol action in the nervous system

There has been a long-standing debate concerning whether alcohols produce their effects in the central nervous system (CNS) by acting on lipids or proteins. Lipid theories postulate that alcohols act via some perturbation of the membrane lipids of CNS neurons, whereas protein theories propose that alcohols act by interacting with a neuronal protein site. Although the primary site of action differs in the two theories, both theories postulate that the CNS effects of alcohols ultimately result from alterations in protein function. This review discusses lipid and protein theories of alcohol action and the evidence supporting these theories. In addition, the effects of alcohols on the function of neurotransmitter-gated ion channels are discussed, as several types of these receptor-ion channels have been found to be sensitive to the actions of alcohols, and recent studies on those actions have yielded new insights into the question of whether the primary action of alcohols involves lipids or proteins.