title: [Excitatory neurotransmission in alcoholism].
abstract: Glutamate is the neurotransmitter at the majority of excitatory synapses in the mammalian CNS. It has been proposed that neurotoxicity linked to chronic alcoholism is mediated primarily by activation of glutamate N-methyl-D-aspartate (NMDA) receptors. Since ethanol stabilizes the membrane potential of NMDA receptors a persistent attenuation of glutamatergic neurotransmission occurs in chronic alcoholism resulting in a compensatory up-regulation of NMDA receptors. Thus, delayed neurotoxicity can be triggered by rebound activation of NMDA receptor-mediated neurotransmission during the withdrawal state. Besides glutamate, homocysteine and excitatory amino acids (EAA) have been shown to act as endogenous agonists at the NMDA receptor and increase excitatory postsynaptic potentials. There is evidence that chronic alcoholism is associated with a derangement in this sulfur amino acid metabolism. These findings indicate the role of hyperhomocysteinemia for withdrawal symptoms, the withdrawal state, and alcoholism-associated brain atrophy. The role of alcoholism-associated hyperhomocysteinemia in respect to NMDA-receptor mediated neurotoxicity and excitotoxicity is discussed.
authors.affiliation: Klinik mit Poliklinik für Psychiatrie und Psychotherapie, Friedrich-Alexander-Universität zu Erlangen-Nuremberg, Erlangen. stefan.bleich@psych.imed.uni.erlangen.de
authors.forename: S
authors.initials: S
authors.lastname: Bleich
authors.forename: W
authors.initials: W
authors.lastname: Sperling
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
authors.forename: J M
authors.initials: JM
authors.lastname: Maler
authors.forename: J
authors.initials: J
authors.lastname: Kornhuber
mesh_terms: D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D018846:Excitatory Amino Acids / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006710:Homocysteine / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology*; D011379:Prognosis; D017470:Receptors, Glutamate / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D006710:Homocysteine; D018698:Glutamic Acid