title: Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice.
abstract: 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.
authors.affiliation: Laboratory of Behavioral Neuroscience, Department of Biochemistry, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Kos
authors.forename: P
authors.initials: P
authors.lastname: Popik
authors.forename: M
authors.initials: M
authors.lastname: Pietraszek
authors.forename: D
authors.initials: D
authors.lastname: Schäfer
authors.forename: W
authors.initials: W
authors.lastname: Danysz
authors.forename: O
authors.initials: O
authors.lastname: Dravolina
authors.forename: E
authors.initials: E
authors.lastname: Blokhina
authors.forename: T
authors.initials: T
authors.lastname: Galankin
authors.forename: A Y
authors.initials: AY
authors.lastname: Bespalov
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior; D019417:Hindlimb Suspension / Q000379:methods; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D014326:Tropanes; D007649:Ketamine; C042253:bemesetron