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Interactive effects of subanesthetic ketamine and haloperidol in healthy humans

Authors
  • Krystal, John H.1
  • D’Souza, D. Cyril1
  • Karper, Laurence P.1
  • Bennett, Alexandre1
  • Abi-Dargham, Anissa1
  • Abi-Saab, Danielle2
  • Cassello, Karyn2
  • Bowers Jr., M. B.1
  • Vegso, Sally3
  • Heninger, George R.1
  • Charney, Dennis S.1
  • Bowers, M. B.4
  • 1 Department of Psychiatry, Yale University School of Medicine, Connecticut, USA, US
  • 2 VA Medical Center, West Haven, CT 06516, USA Fax: +1-203-937-3468, e-mail: [email protected], US
  • 3 Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park St, New Haven, CT 06519, USA, US
  • 4 Grace Education Building, 25 Park St, New Haven, CT 06510, USA, US
Type
Published Article
Journal
Psychopharmacology
Publication Date
Jul 01, 1999
Volume
145
Issue
2
Pages
193–204
Identifiers
DOI: 10.1007/s002130051049
Source
Springer Nature
Keywords
License
Yellow

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.

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