Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice

Eur Neuropsychopharmacol. 2006 May;16(4):297-310. doi: 10.1016/j.euroneuro.2005.10.001. Epub 2005 Nov 8.


Phencyclidine and ketamine (but not other NMDA channel blockers, such as memantine) produce psychotomimetic effects. Since unlike memantine, phencyclidine-like compounds show no significant affinity at 5-HT(3) receptors, we investigated if behavioral effects of ketamine could be reduced by 5HT(3) receptor blockade. Ketamine (3-40 mg/kg) produced ataxia, stereotypes and diminished exploratory activity in mice, and reduced prepulse inhibition of acoustic startle response, lowered accuracy in fixed consecutive number and in delayed non-matching-to-sample tasks in rats. The 5HT(3) receptor antagonist MDL 72222 (0.3-3 mg/kg) administration did not reverse any of these deficits and exerted no effects on discriminative stimulus properties of ketamine. In the tail suspension test, both ketamine and MDL 72222 produced anti-immobility effects when given alone (50-66 and 3 mg/kg, respectively) and together (12.5-25 and 1 mg/kg). The present data suggest that 5-HT(3) receptor blockade does not reverse the behavioral deficits of ketamine and may even enhance its certain effects, such as the antidepressant-like action.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Conditioning, Operant / drug effects
  • Discrimination, Psychological / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Exploratory Behavior
  • Hindlimb Suspension / methods
  • Ketamine / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neural Inhibition / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Reaction Time / drug effects
  • Serotonin 5-HT3 Receptor Antagonists*
  • Serotonin Antagonists / pharmacology*
  • Tropanes / pharmacology*


  • Excitatory Amino Acid Antagonists
  • Serotonin 5-HT3 Receptor Antagonists
  • Serotonin Antagonists
  • Tropanes
  • Ketamine
  • bemesetron