title: Lack of restraint-induced increases of brain serotonin metabolism in rats treated with spiperone: relationship with restraint-induced behavioral deficits.
abstract: Spiperone is a potent dopamine (DA) D2, serotonin (5-hydroxy tryptamine, 5-HT) 5-HT(1A) and 5-HT(2A) antagonist. It is used clinically as an antischizophrenic compound. Previous studies have shown that a downregulation of somatodendritic 5-HT(1A) receptor is involved in adaptation to stress. The present study was designed to investigate the effects of spiperone administration on behavioral adaptation to an episode of restraint stress and on brain serotonin metabolism. Spiperone was administered to rats at a dose of 0.25 mg/kg/ml two times a day for two days. Saline or spiperone treated rats were restrained for 2 h on day 2. Effects of restraint on food intake, water intake, growth rate, plus maze and open field activity were monitored on next day. All animals were killed after a restraint period of 2 h on the 3rd day. An episode of 2 h restraint decreased food intake, growth rate and water intake comparably in saline and spiperone treated rats. Open field activity was not altered by restraint stress or spiperone treatment. Plus maze activity decreased by restraint stress in saline but not spiperone treated rats. 5-HIAA levels increased in saline but not spiperone treated rats. The findings are discussed in the context of a role of serotonin and 5-HT(1A) receptor antagonism in adaptation to stress.
authors.affiliation: Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Fouqia
authors.initials: F
authors.lastname: Mushtaq
authors.forename: Sadia
authors.initials: S
authors.lastname: Haider
authors.forename: Tahira
authors.initials: T
authors.lastname: Perveen
authors.forename: Darakhshan J
authors.initials: DJ
authors.lastname: Haleem