title: Evidence for the involvement of the monoaminergic system, but not the opioid system in the antidepressant-like activity of ellagic acid in mice.
abstract: 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 100mg/kg, p.o.), produced a significant reduction in the duration of immobility, with a profile comparable to that of fluoxetine (20mg/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 (50mg/kg, p.o.) was prevented by pretreatment with p-chlorophenylalanine (100mg/kg, i.p., a serotonin synthesis inhibitor), pindolol (10mg/kg, i.p., a β-adrenoceptors blocker/5HT(1A/1B) receptor antagonist), ketanserin (5mg/kg, i.p., a 5HT(2A/2B) receptor antagonist), ondansetron (1mg/kg, i.p., a 5HT(3) receptor antagonist), prazosin (1mg/kg, i.p., an α(1)-adrenoceptor antagonist) and yohimbine (1mg/kg, i.p., an α(2)-adrenoceptor antagonist), but not with naloxone (1mg/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.
authors.affiliation: Department of Pharmacology, Pondicherry Institute of Medical Sciences (P.I.M.S.), Kalapet, Puducherry-605 014, India. drgirish@pimsmmm.net
authors.forename: Chandrashekaran
authors.initials: C
authors.lastname: Girish
authors.forename: Vishnu
authors.initials: V
authors.lastname: Raj
authors.forename: Jayasree
authors.initials: J
authors.lastname: Arya
authors.forename: Sadasivam
authors.initials: S
authors.lastname: Balakrishnan
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D004610:Ellagic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D019417:Hindlimb Suspension / Q000523:psychology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013550:Swimming; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D011957:Receptors, Opioid; D004610:Ellagic Acid; D012701:Serotonin; D004837:Epinephrine