Interactive effects of subanesthetic ketamine and haloperidol in healthy humans (original) (raw)

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.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

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

Authors

  1. John H. Krystal
    You can also search for this author inPubMed Google Scholar
  2. D. Cyril D’Souza
    You can also search for this author inPubMed Google Scholar
  3. Laurence P. Karper
    You can also search for this author inPubMed Google Scholar
  4. Alexandre Bennett
    You can also search for this author inPubMed Google Scholar
  5. Anissa Abi-Dargham
    You can also search for this author inPubMed Google Scholar
  6. Danielle Abi-Saab
    You can also search for this author inPubMed Google Scholar
  7. Karyn Cassello
    You can also search for this author inPubMed Google Scholar
  8. M. B. Bowers Jr.
    You can also search for this author inPubMed Google Scholar
  9. Sally Vegso
    You can also search for this author inPubMed Google Scholar
  10. George R. Heninger
    You can also search for this author inPubMed Google Scholar
  11. Dennis S. Charney
    You can also search for this author inPubMed Google Scholar
  12. M. B. Bowers
    You can also search for this author inPubMed Google Scholar

Additional information

Received: 10 November 1998/Final version: 23 February 1999

Rights and permissions

About this article

Cite this article

Krystal, J., D’Souza, D., Karper, L. et al. Interactive effects of subanesthetic ketamine and haloperidol in healthy humans.Psychopharmacology 145, 193–204 (1999). https://doi.org/10.1007/s002130051049

Download citation