title: Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients.
abstract: Ethanol is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. Ethanol dependence upregulates NMDA receptors and contributes to crosstolerance with selective NMDA receptor antagonists in animals. This study evaluated whether recovering ethanol-dependent patients show evidence of a reduced level of response to the effects of the NMDA receptor antagonist, ketamine. In this double-blind study, 34 recently detoxified alcohol-dependent patients and 26 healthy comparison subjects completed 3 test days involving a 40-min infusion of saline, ketamine 0.1 mg/kg, or ketamine 0.5 mg/kg in a randomized order. Recovering ethanol-dependent patients showed reduced perceptual alterations, dysphoric mood, and impairments in executive cognitive functions during ketamine infusion relative to the healthy comparison group. No attenuation of ketamine-induced amnestic effects, euphoria, or activation was observed. The alterations in NMDA receptor function observed in recovering ethanol-dependent patients may have important implications for ethanol tolerance, ethanol dependence, and the treatment of alcoholism.
authors.affiliation: Department of Veterans Affairs Alcohol Research Center, VA Connecticut Healthcare System (116-A), West Haven, CT, USA. john.krystal@yale.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Ismene L
authors.initials: IL
authors.lastname: Petrakis
authors.forename: Diana
authors.initials: D
authors.lastname: Limoncelli
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Webb
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorgueva
authors.forename: D Cyril
authors.initials: DC
authors.lastname: D'Souza
authors.forename: Nashaat N
authors.initials: NN
authors.lastname: Boutros
authors.forename: Louis
authors.initials: L
authors.lastname: Trevisan
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000523:psychology*; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D016017:Odds Ratio; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013695:Temperance / Q000523:psychology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine