title: Ethanol's inhibition of LTP may not be mediated solely via direct effects on the NMDA receptor.
abstract: Acute abuse of alcohol is well known to have deleterious effects on memory. However, the molecular and cellular bases of this effect are not well understood. Ethanol is known to inhibit long-term potentiation (LTP), a putative cellular substrate of memory. However, there is controversy concerning the doses of ethanol required for inhibition of LTP. We examined the doses of ethanol required to inhibit LTP in the CA1 region of the hippocampus. We used two different LTP-inducing paradigms in these studies and found that only doses of ethanol associated with profound intoxication (50-100 mM) can produce significant inhibition of LTP. We also investigated the molecular mechanisms of ethanol's effect on LTP. Activation of the N-methyl-D-aspartate receptor plays a critical role in LTP, and ethanol has been shown to partially inhibit N-methyl-D-aspartate receptor function. We tested directly whether the level of N-methyl-D-aspartate inhibition produced by 100 mM ethanol is sufficient to account for the complete inhibition of LTP produced by 100 mM ethanol. Our data suggest that ethanol's effects on the N-methyl-D-aspartate receptor can account for most, but not all of ethanol's inhibition of LTP.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schummers
authors.forename: S
authors.initials: S
authors.lastname: Bentz
authors.forename: M D
authors.initials: MD
authors.lastname: Browning
mesh_terms: D000435:Alcoholic Intoxication / Q000503:physiopathology; D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol