Fouqia Mushtaq, Saida Haider, Tahira Perveen, Darakhshan J Haleem.
Lack of restraint-induced increases of brain serotonin metabolism in Rats treated with Spiperone: relationship with restraint-induced behavioral deficits.
Pak J Pharm Sci Jan ;17(2):57-65.

Spiperone is a potent dopamine (DA) D2, serotonin (5-hydroxy tryptamine, 5-HT) 5HT1A and 5-HT2A antagonist. It is used clinically as an antischizophrenic compound. Previous studies have shown that a downregulation of somatodendritic 5-HT1A 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 heated rats were restrained for 2h 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 2h on the 3rd day. An episode of 2h 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-HT1A receptor antagonism in adaptation to stress.

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