N-methyl-D-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability.
This review takes a translational neuroscience perspective on the role of glutamate systems in human ethanol abuse and dependence. Ethanol is a simple molecule with profound effects on many chemical systems in the brain. Glutamate is the primary excitatory neurotransmitter in the brain. Glutamatergic systems are targets for the actions of ethanol via its antagonism of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor and other mechanisms. The modulation of glutamatergic function by ethanol contributes to both euphoric and dysphoric consequences of ethanol intoxication. Adaptations within glutamatergic systems appear to contribute to ethanol tolerance and dependence and to both acute and protracted features of ethanol withdrawal. Perhaps because of the important glutamatergic mediation of the behavioral effects of ethanol, glutamatergic systems appear to contribute to the vulnerability to alcoholism, and novel glutamatergic agents may play a role in the treatment of ethanol abuse and dependence.
Krystal
John H
JH
NIAAA Center for the Translational Neuroscience of Alcoholism, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. john.krystal@yale.edu
Petrakis
Ismene L
IL
Mason
Graeme
G
Trevisan
Louis
L
D'Souza
D Cyril
DC
D000428:Alcohol Drinking / Q000009:adverse effects / Q000523:psychology; D000437:Alcoholism / Q000378:metabolism / Q000523:psychology / Q000628:therapy; D000818:Animals; D002986:Clinical Trials as Topic; D004198:Disease Susceptibility; D000431:Ethanol / Q000009:adverse effects; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology*; D012201:Reward; D012307:Risk Factors; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol