Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients.
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.
Krystal
John H
JH
Department of Veterans Affairs Alcohol Research Center, VA Connecticut Healthcare System (116-A), West Haven, CT, USA. john.krystal@yale.edu
Petrakis
Ismene L
IL
Limoncelli
Diana
D
Webb
Elizabeth
E
Gueorgueva
Ralitza
R
D'Souza
D Cyril
DC
Boutros
Nashaat N
NN
Trevisan
Louis
L
Charney
Dennis S
DS
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*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine