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Background: In some disorders such as diabetes mellitus patients can display depressive symptoms. Metformin is among the first-line treatments for management of the type 2 diabetes mellitus which may have some anti-depressant effect. Objective: Current investigation was performed to examine the anti-depressant effects of metformin and the involvement of nitric oxide (NO) in this way, in an experimental animal model of cholestasis in NMRI (Naval Medical Research Institute) mice. Materials and Methods: Bile duct ligated (BDL) and sham-operated mice were forced to swim separately and the effect of metformin on immobility time in the last 4 minutes of the 6 minutes test was assessed. To evaluate the probable participation of NO, N-nitro-L-arginine methyl ester (L-NAME) a non-specific NO synthase inhibitor and aminoguanidine, a specific iNO synthase inhibitor were injected acutely to metformin-treated BDL mice and then their immobility time was calculated in forced swimming test (FST). Results: The immobility time significantly reduced after bile-duct ligation and metformin-treatment decreased this time additionally. L-NAME but not amino-guanidine administration significantly inhibited antidepressant like property of metformin in BDL mice. We have displayed that NO overproduction by metformin in cholestatic mice produce an anti-depressant like effect, causing a decrease in the mice immobility time in FST. Conclusion: Metformin pretreatment can decrease depression in cholestatic mice through an NO dependent pathway.

Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100% of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P

Dichlorvos, a synthetic organophosphate toxin, is used as pesticides. These toxins can be used as pesticides in farming and medicine for the devastation and/or elimination of ectoparasites of animals. Reports have shown that Dichlorvos generate seizure effects in various animals. Potassium channel opener is extensively used for medication of cardiovascular and other diseases. Studies have shown that potassium channel opener has anticonvulsant effects in different animal models. The goal of this study was to evaluate the effect of dizoxide on Dichlorvos-induced seizures in mice. In this research, the animals received different doses of Diazoxide (1, 2.5, 5, 10, and 20 mg/kg b.wt.) intraperitoneally 30 min before intraperitoneal injection of Dichlorvos (50 mg/kg b.w.t). After Dichlorvos injection, latency of clones, severity of seizure, and finally death as the fate were investigated. Results showed that Diazoxide dose-dependently decreased the severity of Dichlorvos-induced seizures, so that Diazoxide at a dose of 5 mg (the lowest, P