The selective 5-HT(6) receptor antagonist Ro 04-6790 attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801.
There are experimental evidences indicating that the non-competitive NMDA receptor antagonist MK-801 impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hypermotility, stereotypies and ataxia). The present study was designed to investigate the efficacy of the selective 5-HT(6) receptor antagonist Ro 04-6790 in counteracting these MK-801-induced behavioural effects in the rat. The effects of Ro 04-6790 in antagonizing MK-801-induced memory deficits were assessed using the object recognition task. The ability of this 5-HT(6) receptor antagonist in counteracting hypermotility, stereotypies and ataxia produced by MK-801 were evaluated in a motor activity cage. Post-training administration of Ro 04-6790 (10 and to some extent also 3mg/kg) antagonized MK-801-induced performance deficits in a recognition memory test. In a subsequent study, Ro 04-6790 (3 and 10 mg/kg) reversed hypermotility and ataxia produced by MK-801. This 5-HT(6) receptor antagonist also alleviated MK-801-induced certain stereotypies. Our findings indicate that Ro 04-6790 attenuates behavioural effects related to the hypofunction of the NMDA receptor suggesting that this compound might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists.
Pitsikas
Nikolaos
N
Department of Pharmacology, School of Medicine, University of Thessaly, Larissa, Greece. npitsikas@med.uth.gr
Zisopoulou
Styliani
S
Pappas
Ioannis
I
Sakellaridis
Nikolaos
N
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D009043:Motor Activity / Q000187:drug effects; D010364:Pattern Recognition, Visual / Q000187:drug effects; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
D016291:Dizocilpine Maleate; D011743:Pyrimidines; D012702:Serotonin Antagonists; C114163:Ro 4-6790; D000096926:Benzenesulfonamides