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

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-HT3 receptors, we investigated if behavioral effects of ketamine could be reduced by 5HT3 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 5HT3 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-HT3 receptor blockade does not reverse the behavioral deficits of ketamine and may even enhance its certain effects, such as the antidepressant-like action.