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 receptor agonist which crosses the blood brain barrier, on three rodent models in which antidepressants are active. In the forced swimming test, SR 57227A dose-dependently reduced the duration of immobility in mice and rats after i.p. administration. (ED50 = 14.2 mg/kg i.p. in mice, and 7.6 mg/kg i.p. in rats.) The compound was also active in both species after oral administration. In a time-course study in mice, SR 57227A (20 mg/kg p.o.) produced a significant effect lasting 6 h. SR 57227A (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 days 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 receptors can produce antidepressant-like effects in behavioral tests in rodents.
Poncelet
M
M
Sanofi Recherche, Montpellier, France.
Perio
A
A
Simiand
J
J
Gout
G
G
Soubrie
P
P
Le Fur
G
G
D000374:Aggression / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006380:Helplessness, Learned; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D010880:Piperidines; D017366:Serotonin Receptor Agonists; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride