Methanolic fraction from Tamala (Diospyros montana Roxb.) ameliorates anxiety like behaviour via 5-HT2A pathway in rats

•Methanolic extract of Diospyros montana showed anxiolytic activity in experimental rats.•The extracts increased serotonergic neurotransmitters level in the amygdala.•Extracts exhibited increased GABA level in the amygdala. D. montana (Roxb.) is a medicinal plant cultivated throughout Eastern Asia, comprises several biologically active compounds, such as steroids, naphthoquinones, polyphenols, and flavonoids. Earlier reports revealed that D. montana has been used for anti-inflammatory, antiviral, anticancer, inhibitor of prostaglandin synthesis, hypolipidemic, and antileukemic agent. However, the anxiolytic activity of D. montana yet not explained. Therefore, the objective of this study is to investigate the anxiolytic effect of the methanolic extract of powder extracted from D. montana (Roxb.) leaves. The anxiolytic activity was evaluated in an open-field test (OFT), hole board test (HBT) and elevated plus maze test (EPM). The rats received an oral pre-treatment of methanolic extract of Diospyros montana (MDM) (50, 100, 200 mg/kg; p.o.) for 7 days and the anxiolytic activity were estimated in experimental rat models. MDM (100 and 200 mg/kg) and diazepam increased behaviour parameters in hole board test in terms of head-dip, a ratio of head-dip/sniffing, and decreased sniffing activity. Further, MDM (100 and 200 mg/kg) and diazepam increased behavioural performance in the EPM and OFT test paradigm. Treatment with MDM (100 and 200 mg/kg) and diazepam increased serotonin level and mRNA expression of the 5-HT2A receptor in the amygdala of experimental rats. In an additional set of experiments, in OFT, HBT and EPM studies, flumazenil attenuated the anxiolytic effect of the minimum effective dose of MDM (100 mg/kg), suggesting the mechanism mediated by the GABAA receptor. Furthermore, MDM-100 mg/kg has shown a lack of sedative-like effect relative to diazepam (6 mg/kg, p.o.) in the OFT and EPM test paradigm. The present findings indicate that anxiolytic effect of MDM may involve GABA and serotonin mediated mechanisms, and MDM can be a potential therapeutic agent for the management of anxiety illustrated in fig-11. [Display omitted]