Evaluation of the role of monoaminergic and nonmonoaminergic systems in the psychotropic effects of morin in mice: an interaction study with receptor blockers

Abstract

Treatment-resistance depression and memory impairment disease, burdened with high levels of serious adverse effects of currently existing antidepressants and memory enhancers, have necessitated the search for alternative agents. Although previous preclinical studies have revealed the antidepressant-like and memory-enhancing potentials of morin, a compound isolated from Morus alba, the neurotransmitter receptor interaction mechanisms of action remain unknown. Hence, the role of monoaminergic and nonmonoaminergic neurotransmitter receptors in the antidepressant-like and memory-enhancing effects in naive mice were evaluated in this study. Male Swiss mice were pretreated intraperitoneally with D2-dopaminergic receptor antagonists (haloperidol), 5-HT1- and 5-HT2-receptor antagonist (metergoline), 5-HT synthesis inhibitor (para-chlorophenylalanine), α1-noradrenoceptor antagonist (prazosin), α2-noradrenoceptor antagonist (yohimbine), or cholinergic receptor antagonist (atropine) prior to the administration of morin (100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.). The memory-enhancing and antidepressant-like effects were then evaluated 30 min later using the open-field test (OFT), Y-maze test (YMT), and forced swim test (FST). Morin reduced locomotor activity however, it was reversed by metergoline, pCPA, prazosin, yohimbine, haloperidol, and atropine independent of their actions. Morin exhibited antidepressant property in the FST when compared with control (p < 0.05). Metergoline, para-chlorophenylalanine, prazosin, and haloperidol decreased the antidepressant-like activity of morin. Morin showed memory-enhancing effect in the YMT relative to control. Pretreatment with metergoline, para-chlorophenylalanine, or atropine, however, decreased the memory-promoting effect of morin. These findings suggest that the antidepressant-like activity exhibited by morin might be mediated via interactions with 5-HTergic, noradrenergic, and dopaminergic receptors, while the memory-enhancing effect might involve interaction with both 5-HTergic and cholinergic receptors.