Kos T, Popik P, Pietraszek M, Schäfer D, Danysz W, Dravolina O, Blokhina E, Galankin T, Bespalov A Y
Laboratory of Behavioral Neuroscience, Department of Biochemistry, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
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.