Dose-response characteristics of intravenous ketamine on dissociative stereotypy, locomotion, sensorimotor gating, and nociception in male Sprague-Dawley rats

Kennett D. Radford, Thomas Y. Park, Bong Hyo Lee, Sean Moran, Lisa Osborne Smith, Kwang H. Choi

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Clinicians administer subanesthetic intravenous (IV) ketamine infusions for treatment of refractory depression, chronic pain, and post-traumatic stress disorder in humans. However, ketamine is administered via the subcutaneous (SC) or intraperitoneal (IP) routes to rodents in most pre-clinical research, which may limit translational application. The present study characterized the dose-response of a subanesthetic IV ketamine bolus (2 and 5 mg/kg) and 1-h infusion (5, 10, and 20 mg/kg/h) on dissociative stereotypy, locomotion, sensorimotor gating, and thermal nociception in male Sprague-Dawley rats. The secondary aim was to measure ketamine and norketamine plasma concentrations following IV ketamine bolus at 1, 20, and 50 min and at the conclusion of the 1-h infusion using liquid chromatography/mass spectrometry. The results showed that ketamine bolus and infusions produced dose-dependent dissociative stereotypy. Bolus (2 and 5 mg/kg) and 20 mg/kg/h infusion increased locomotor activity while 5 mg/kg/h infusion decreased locomotor activity. Both 10 and 20 mg/kg/h infusions reduced the acoustic startle reflex, while 5 mg/kg bolus and 20 mg/kg/h infusion impaired pre-pulse inhibition. Ketamine 5 mg/kg bolus and the 10 and 20 mg/kg/h infusions induced significant and prolonged antinociception to the hotplate test. Plasma concentrations of ketamine decreased quickly after bolus while norketamine levels increased from 1 to 20 min and plateaued from 20 to 50 min. The peak ketamine plasma concentrations [ng/ml] were similar between 5 mg/kg bolus [4100] vs. 20 mg/kg/h infusion [3900], and 2 mg/kg bolus [1700] vs. 10 mg/kg/h infusion [1500]. These results support the findings from previous ketamine injection studies and further validate the feasibility of administering subanesthetic doses of IV ketamine infusion to rats for neuropharmacological studies.

Original languageEnglish (US)
Pages (from-to)130-140
Number of pages11
JournalPharmacology Biochemistry and Behavior
Volume153
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

Keywords

  • Antinociception
  • Dissociative stereotypy
  • Intravenous
  • Ketamine
  • Locomotor activity
  • Rat
  • Sensorimotor gating

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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