Alcohol Actions on Glutamate Receptors

Abstract

Alcohol is arguably the oldest drug known to man, its use dating back at least 10,000 yr to the dawn of human civilization (1). Although illicit drug use often receives more attention in contemporary society, alcohol abuse exacts a devastating toll: In the United States at present, over 7% of the population meet diagnostic criteria for alcohol abuse or alcoholism (2), over 28% of children under 18 yr of age are exposed to alcohol abuse or dependence in the home (3), and the overall economic cost to society of alcohol abuse has been estimated at $ 185 billion (4). Despite intensive research since the latter part of the previous century, it is clear that the biological actions that are responsible for the characteristic effects of ethyl alcohol, or ethanol, on human physiology and behavior are still incompletely understood. Because of the simple chemical structure of ethanol (it differs from water only by two methylene groups) and its low potency (it produces most of its biological effects at millimolar concentrations), alcohol undoubtedly interacts with multiple sites in the central nervous system. The biological effects of alcohol almost certainly reflect its concerted actions at a number of these sites. Of the many possible targets of alcohol actions, neurotransmitter receptors, and in particular, neurotransmitter-gated receptor-ion channels are currently believed to be among the most important (5). Because the neurotransmitter glutamate mediates the majority of fast excitatory neurotransmission in the central nervous system via actions on glutamate-gated receptor-ion channels (6), effects of alcohol on these ion channels could profoundly alter central nervous system function.