ORIGINAL INVESTIGATION

Psychopharmacology

, Volume 145, Issue 2, pp 193-204

First online:

Interactive effects of subanesthetic ketamine and haloperidol in healthy humans

  • John H. KrystalAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
  • , D. Cyril D’SouzaAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
  • , Laurence P. KarperAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
  • , Alexandre BennettAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
  • , Anissa Abi-DarghamAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
  • , Danielle Abi-SaabAffiliated withVA Medical Center, West Haven, CT 06516, USA Fax: +1-203-937-3468, e-mail: john.krystal@yale.edu
  • , Karyn CasselloAffiliated withVA Medical Center, West Haven, CT 06516, USA Fax: +1-203-937-3468, e-mail: john.krystal@yale.edu
  • , M. B. Bowers Jr.Affiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
  • , Sally VegsoAffiliated withAbraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park St, New Haven, CT 06519, USA
    • , George R. HeningerAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
    • , Dennis S. CharneyAffiliated withDepartment of Psychiatry, Yale University School of Medicine, Connecticut, USA
    • , M. B. BowersAffiliated withGrace Education Building, 25 Park St, New Haven, CT 06510, USA

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Abstract

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with prominent psychoactive effects in humans. This study evaluated whether the oral administration of haloperidol 5 mg would block the effects of an intravenous ketamine infusion (bolus of 0.26 mg/kg followed by 0.65 mg/kg per hour). Twenty healthy subjects completed 4 test days involving the oral administration of haloperidol or matched placebo 2 h prior to the intravenous infusion of ketamine or saline. Ketamine produced cognitive, behavioral, neuroendocrine, and physiologic effects in the healthy subjects that were similar to previous reports. Haloperidol pretreatment reduced impairments in executive cognitive functions produced by ketamine as measured by proverb interpretations and the Wisconsin Card Sorting Test. However, it failed to block the capacity of ketamine to produce psychosis, perceptual changes, negative symptoms, or euphoria in healthy subjects. These data outline an important, but functionally delineaeted modulation of ketamine effects by dopamine2 receptors and other sites of haloperidol action.

Key words Ketamine N-Methyl-D-asparate Glutamate Psychosis Dissociation Addiction Dopamine Neuroleptic Memory Attention Frontal cortex Extrapyramidal symptom Wisconsin Card Sorting Test