Antidepressant, anxiolytic, and anticataleptic effects of aqueous leaf extract of Antiaris toxicaria Lesch. (Moraceae) in mice: possible mechanisms of actions.

Abstract Background: The leaves of Antiaris toxicaria Lesch. (Moraceae) are used by traditional medicine practitioners in southwest Nigeria in the management of epilepsy, wounds, and neurological disorders. Hence, this study was undertaken to investigate the effect of the aqueous leaf extract of A. toxicaria on the central nervous system. Methods: One hour after administration of A. toxicaria [50-300 mg/kg orally (p.o.)], its antidepressant effect was evaluated using the forced swimming test (FST), anxiolytic effect using elevated plus maze (EPM) test, and anticataleptic effect using haloperidol-induced catalepsy, whereas its effects on hypnosis and motor coordination were studied using hexobarbitone-induced sleeping time and open-field tests, respectively, in mice. Results: Antiaris toxicaria (300 mg/kg) significantly increased swimming activity (36.88%) and reduced immobility time (38.54%). Pretreatment of mice with prazosin (an α1-adrenoceptor antagonist), sulpiride (a D2 receptor antagonist), and l-NG-nitro-arginine (nitric oxide synthase inhibitor) 15 min before A. toxicaria (300 mg/kg p.o.) treatment significantly prevented its antidepressant-like effect by 35.58%, 53.30%, and 56.11%, respectively, in the FST. However, pretreatment with metergoline (5-HT2 receptor antagonist), and atropine (muscarinic cholinergic antagonist) failed to reverse this effect. Interestingly, A. toxicaria (50 mg/kg) significantly increased open-arm exploration in the EPM by 70.31%, which was reversed by 82.66% in the presence of flumazenil [3 mg/kg intraperitoneally (i.p.)]. Haloperidol (1 mg/kg i.p.) induced cataleptic behavior in mice, which was reversed by A. toxicaria (300 mg/kg) (p<0.001) treatment. Conclusions: The results suggest that A. toxicaria possesses an antidepressant-like effect involving interaction with α1-adrenoceptor, D2 dopamine receptor, and nitrergic pathway; an anxiolytic-like effect linked to the benzodiazepine system; and a neuroprotective effect.