The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jul 1994
Comparative StudyDifferential induction of 5-HT1A-mediated responses in vivo by three chemically dissimilar 5-HT1A agonists.
In the rat, activation of 5-hydroxytryptamine1A (5-HT1A) receptors causes hypothermia and the 5-HT syndrome. The effects of three chemically dissimilar 5-HT1A agonists administered s.c. [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), gepirone, and (+)4-[n-5-(methoxychroman-3-yl)n-propylamino]butyl-8-azaspiro++ +[4,5] decane-7,adione ((+) S-20499)] on both of these responses were studied. The same maximal drop in body temperature (approximately 2.5 degrees C) was elicited by all three agonists, 8-OH-DPAT being the most potent (EC50 = 0.05 mg/kg), followed by gepirone (1.8 mg/kg) and (+) S-20499 (8 mg/kg). ⋯ This indicates that forepaw treading, like hypothermia, is mediated by activation of 5-HT1A receptors. Gepirone (5-10 mg/kg) attenuated the forepaw treading induced by either 8-OH-DPAT (4 mg/kg) or 5-MeODMT (5 mg/kg); by contrast, (+) S-20499, at doses up to 75 mg/kg, did not attenuate the forepaw treading induced by either 8-OH-DPAT or 5-MeODMT. The inability of (+) S-20499 either to induce the 5-HT syndrome or forepaw treading or to attenuate the forepaw treading induced by other agonists could be due to several factors, one of which is that different subtypes of the 5-HT1A receptor mediate hypothermia and the 5-HT syndrome.