ANTIDEPRESSANT-LIKE EFFECTS OF SR 57227A, A 5-HT3 RECEPTOR AGONIST, IN RODENTS

We have investigated the effect of SR 57227A, a selective 5-HT3 recept or agonist which crosses the blood brain barrier, on three rodent mode ls in which antidepressants are active. In the forced swimming test, S R 57227A dose-dependently reduced the duration of immobility in mice a nd rats after i.p. administration. (ED(50) = 14.2 mg/kg i.p. in mice, and 7.6 mg/kg i.p. in rats.) The compound was also active in both spec ies after oral administration. In a time-course study in mice, SR 5722 7A (20 mg/kg p.o.) produced a significant effect lasting 6 h. SR 57227 A (1 and 3 mg/kg i.p.) reduced the elevation of the escape failures in the learned helplessness model in rats by 50-60% on the last two daps of the avoidance task, and reduced isolation-induced aggressivity in mice by 50 to 85%, an effect which was antagonised by zacopride (1 mg/ kg i.p.). These results suggest that the stimulation of 5-HT3 receptor s can produce antidepressant-like effects in behavioural tests in rode nts.