Psychopharmacology

, Volume 145, Issue 2, pp 193–204

Interactive effects of subanesthetic ketamine and haloperidol in healthy humans

  • John H. Krystal
  • D. Cyril D’Souza
  • Laurence P. Karper
  • Alexandre Bennett
  • Anissa Abi-Dargham
  • Danielle Abi-Saab
  • Karyn Cassello
  • M. B. Bowers Jr.
  • Sally Vegso
  • George R. Heninger
  • Dennis S. Charney
  • M. B. Bowers
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130051049

Cite this article as:
Krystal, J., D’Souza, D., Karper, L. et al. Psychopharmacology (1999) 145: 193. doi:10.1007/s002130051049

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 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • John H. Krystal
    • 1
  • D. Cyril D’Souza
    • 1
  • Laurence P. Karper
    • 1
  • Alexandre Bennett
    • 1
  • Anissa Abi-Dargham
    • 1
  • Danielle Abi-Saab
    • 2
  • Karyn Cassello
    • 2
  • M. B. Bowers Jr.
    • 1
  • Sally Vegso
    • 3
  • George R. Heninger
    • 1
  • Dennis S. Charney
    • 1
  • M. B. Bowers
    • 5
  1. 1.Department of Psychiatry, Yale University School of Medicine, Connecticut, USAUS
  2. 2.VA Medical Center, West Haven, CT 06516, USA Fax: +1-203-937-3468, e-mail: john.krystal@yale.eduUS
  3. 3.Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park St, New Haven, CT 06519, USAUS
  4. 4.Department of Neurology, Cornell University Medical Center, New York, USAUS
  5. 5.Grace Education Building, 25 Park St, New Haven, CT 06510, USAUS
  6. 6.New York State Psychiatric Institute, 722 W, 168th St, New York, NY 10032, USAUS

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