Glutamate receptor changes in brain synaptic membranes during chronic alcohol intake.
Ethanol inhibits the receptor-ion channels activated by the glutamate analog N-methyl-D-aspartate (NMDA) in mammalian brain neurons. The high degree of sensitivity of these receptors to the acute effects of ethanol has led to the development of hypotheses that brain neurons may adapt to chronic exposure to ethanol either by increasing the numbers of NMDA receptors, or by expressing receptors with decreased sensitivity to ethanol, or by expressing receptors with increased affinity for the endogenous activator of these entities, L-glutamic acid. Studies performed with experimental animal models of chronic ethanol intake are indicative of an adaptive response that entails the expression in neuronal membranes of greater numbers of L-glutamate and NMDA receptors. When similar studies were performed with synaptic membranes isolated from the brains of human alcoholics, there was an apparent increase in the total number of glutamate receptors, but a decrease in the density of the subpopulation of these receptors that are activated by NMDA. These results are interpreted to suggest that there are more subtle and complex adaptations made in neurons in the brains of human alcoholics as compared with those occurring in animal models of chronic alcoholism.
Michaelis
E K
EK
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045, USA.
Michaelis
M L
ML
Freed
W J
WJ
Foye
J
J
D000222:Adaptation, Physiological; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol