Evidence for the involvement of the monoaminergic system, but not the opioid system in the antidepressant-like activity of ellagic acid in mice

Dietary flavonoids possess a multiplicity of neuroprotective actions in various central nervous pathophysiological conditions including depression. Ellagic acid is a polyphenolic compound that occurs in plants such as raspberries, nuts and eucalyptus species. The present study was designed to investigate the antidepressant-like effect of ellagic acid in mice using forced swimming test (FST) and tail suspension test (TST). The involvement of the monoaminergic and opioid systems in the antidepressant-like activity of ellagic acid was also studied. Our results showed that ellagic acid when administered acutely or chronically to mice (25, 50 and 100 mg/kg, p.o.), produced a significant reduction in the duration of immobility, with a profile comparable to that of fluoxetine (20 mg/kg, p.o.). However, ellagic acid treatment had no effect on the locomotor activity of mice when tested in actophotometer. The reduction in immobility time observed with ellagic acid treatment (50 mg/kg, p.o.) was prevented by pretreatment with p-chlorophenylalanine (100 mg/kg, i.p., a serotonin synthesis inhibitor), pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5HT(1A/1B) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5HT(2A/28) receptor antagonist), ondansetron (1 mg/kg, i.p., a 5HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist) and yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), but not with naloxone (1 mg/kg, i.p., an opioid receptor antagonist). Our results suggest that ellagic acid produced an antidepressant-like effect which was unrelated to its locomotor activity. Furthermore, this anti-immobility effect seems most likely to be mediated through an interaction with the monoaminergic system (serotonergic and noradrenergic systems) and not through the opioid system. (C) 2012 Elsevier B.V. All rights reserved.