ro-4-6790 and Mental-Disorders

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.

Topics: Analysis of Variance; Animals; Behavior, Animal; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Interactions; Exploratory Behavior; Male; Mental Disorders; Motor Activity; Pattern Recognition, Visual; Pyrimidines; Rats; Rats, Wistar; Serotonin Antagonists