Chcbulinic acid potentiates antideprcssant-like properties through nionoaininergic systems and adult hippocampal neurogenesis in laboratory mice

Abstract

Background: Chcbulinic acid, an ellagitannin, present in the fruits of Terminalia chehula has been reported to show antioxidant, anti-nociceptive and antidepressant properties. Pre-clinical and clinical studies have suggested the involvement t of monoamines, particularly the serotonergic and noradrenergic systems in the molecular mechanism of depression. Research has also suggested that the mod e o f action of antidepressants may be via hippocampal neurogenesis. There is no report elucidating how chcbulinic acid potentiates its antidepressant properties. This study was therefore carried out to investigate its probable antidepressant mechanisms of action. Methods: Involvement of serotonergic, cholinergic, dopaminergic and adrenergic systems were studied using Forced Swimming Test, Tail Suspension Test (as models of depression) and Open Field Test which measures ambulatory behaviors. Antagonists Prazosin, an alpha 1-adrenergic receptor blocker (62.5 M&/kg, mctcrgolinc, a 5HT, receptor blocker (4 mg/kg, //>.), atropine, a -muscarinic cholinergic receptor blocker (1 mg/kg and sulpiride, a dopaminergic, receptor blocker (50 mg/ kg /'./;) were administered before chcbulinic acid (20 mg/kg). Animals were also treated with chcbulinic acid for 7, 21 and 28 days to see the effect of continuous administration, after which neuronal ecll proliferation in the hippocampus was determined by Immunohistochemistry using Ki-67 antibody. Results: Results showed that mobility was reversed in animals pre-treated with mctcrgolinc significantly (/) < 0.05), but not sulpiride, prazosin and atropine, showing a possible involvement of serotoninergic system. There is a marked increase in the number of proliferating neuronal cells as observed after chronic treatment with chcbulinic acid.