Indorenate produces antidepressant-like actions in the rat forced swimming test via 5-HT1A receptors

Abstract Rationale. Indorenate has been proposed to possess antihypertensive, anorectic, stimulus control and anxiolytic-like actions. This compound has affinity mainly for the serotonergic_1A/1B receptors, hence it could possess antidepressant-like activity. Objectives. The general purpose of this study was to explore the possible antidepressant-like effects of the serotonergic compound indorenate in the forced swimming test (FST). Methods. In a first approach, a comparison of the actions of several doses of indorenate (2.5, 5.0, 10 mg/kg) with those of other 5-HT_1A agonists, buspirone (5.0, 10.0 mg/kg) and 8-OH-DPAT (0.25, 0.50, 1.0 mg/kg), was performed in the FST. Secondly, in order to determine the serotonergic receptors that are participating in indorenate's action, different doses of serotonergic antagonists were administered. The compounds used were the 5-HT_1A/1B and β-adrenergic antagonist pindolol (2.5, 5.0 mg/kg), the 5-HT_1B receptor antagonist GR 55562 (0.75, 1.5, 3.0 mg/kg), the 5-HT_1A antagonist WAY 100635 (0.25, 0.5, 1.0 mg/kg) and the 5-HT₂ antagonist ketanserin (1.0, 2.0, 4.0 mg/kg). Results. Indorenate (10 mg/kg), 8-OH-DPAT (1.0 mg/kg) and buspirone (5.0 and 10.0 mg/kg) reduced immobility behaviour in the FST, considered as an antidepressant-like effect. Both doses of pindolol (2.5 and 5.0 mg/kg) and WAY 100635 (0.5 and 1.0 mg/kg) antagonised the antidepressant-like effect of indorenate. Neither 5-HT_1B (GR55562) nor 5-HT₂ (ketanserin) antagonists produced changes in the effect of indorenate in the FST. Conclusions. Indorenate produces antidepressant-like actions in the FST that are mediated by the stimulation of 5-HT_1A receptors. Electronic Publication