The role of glutamatergic neurotransmission in the pathophysiology of alcoholism.
Recent evidence suggests that ethanol abuse produces its diverse effects on the brain to a substantial degree by disrupting the function of the major excitatory neurotransmitter, glutamate. Ethanol, at concentrations associated with behavioral effects in humans, inhibits the N-methyl-D-aspartate (NMDA) receptor, which mediates the post-synaptic excitatory effects of glutamate. Tolerance to ethanol results in up-regulation of the NMDA receptor so that abrupt withdrawal produces a hyperexcitable state that leads to seizures, delerium tremens, and excitotoxic neuronal death. Ethanol's inhibition of the NMDA receptor in the fetal brain likely contributes to the CNS manifestations of fetal alcohol syndrome. Therapeutic strategies aimed at correcting glutamatergic dysregulation in alcoholism need to be explored.
Tsai
G
G
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Boston, USA.
Coyle
J T
JT
D000430:Alcohol Withdrawal Delirium / Q000209:etiology; D000437:Alcoholism / Q000188:drug therapy / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000196:embryology; D016923:Cell Death; D002492:Central Nervous System Depressants / Q000009:adverse effects; D000431:Ethanol / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology / Q000503:physiopathology; D018698:Glutamic Acid / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000009:adverse effects; D018377:Neurotransmitter Agents / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid