title: Effects of the novel 5-HT1A receptor antagonist, (+)-WAY 100135, on stereotyped behaviour induced by the NMDA receptor antagonist dizocilpine in rats.
abstract: We have recently shown that the stereotyped behaviour induced by the uncompetitive NMDA receptor antagonist dizocilpine (MK-801) can be attenuated or blocked by partial agonists at 5-HT receptors of the 5HT1A subtype, indicating that 5-HT (5-hydroxytryptamine, serotonin) is involved in the stereotyped behaviour produced by dizocilpine. In the present experiment, a selective, silent 5-HT1A receptor antagonist, (+)-WAY 100135 (N-tert-butyl 3-4(2-methoxyphenyl) piperazin 1-yl-2-phenylpropanamide dihydrochloride), was used to further study the role of 5-HT activation in dizocilpine-induced behaviours. At a dose of 10 mg/kg, (+)-WAY 100135 significantly reduced the intensity of head weaving induced by dizocilpine, but this effect was lost by increasing the dose to 20 mg/kg. At this higher dose, (+)-WAY 100135 induced marked but short-lasting increases in skeletal muscle tone and hindlimb abduction, resembling components of the '5-HT behavioural syndrome', which would explain its biphasic effects on dizocilpine induced behaviours. The data substantiate that, in addition to the well known activation of dopaminergic transmission, activation of the 5-HT system might be involved in the behavioural effects of NMDA receptor antagonists such as dizocilpine.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Löscher
authors.forename: D
authors.initials: D
authors.lastname: Hönack
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists; D012737:Sex Factors; D013239:Stereotyped Behavior / Q000187:drug effects*
chemical_list: D010879:Piperazines; D012702:Serotonin Antagonists; C081293:WAY 100135; D016291:Dizocilpine Maleate