title: Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: involvement of monoaminergic system.
abstract: BACKGROUND
  The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST.
  
  
  METHODS
  HeAC (25-400mg/kg, p.o.) was administered 1h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15min before oral administration of HeAC (200mg/kg) to mice and 1h thereafter, subjected to FST.
  
  
  RESULTS
  HeAC (200 and 400mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), and GR 127993 (5-HT1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5mg/kg, p.o.) or fluoxetine (5mg/kg, p.o.), with HeAC (25mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST.
  
  
  CONCLUSIONS
  The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D1 and D2), noradrenergic (α1 and α2 adrenoceptors), and serotonergic (5HT1B receptors) systems. Also, the potentiation of the anti-immobility effect of conventional antidepressants (fluoxetine and imipramine) by Alchornea cordifolia suggest potential therapeutic effect in depression.
authors.affiliation: Department of Pharmacology, Therapeutics, and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003 Surulere, Lagos, Nigeria.
authors.forename: Ismail O
authors.initials: IO
authors.lastname: Ishola
authors.affiliation: Department of Pharmacology, Therapeutics, and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003 Surulere, Lagos, Nigeria. Electronic address: eoagbaje@cmul.edu.ng.
authors.forename: Esther O
authors.initials: EO
authors.lastname: Agbaje
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, Lagos, Nigeria.
authors.forename: Moshood O
authors.initials: MO
authors.lastname: Akinleye
authors.affiliation: Department of Pharmacology, Therapeutics, and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003 Surulere, Lagos, Nigeria.
authors.forename: Chris O
authors.initials: CO
authors.lastname: Ibeh
authors.affiliation: Department of Pharmacology, Therapeutics, and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003 Surulere, Lagos, Nigeria.
authors.forename: Olufunmilayo O
authors.initials: OO
authors.lastname: Adeyemi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000502:physiology*; D000431:Ethanol / Q000737:chemistry; D019665:Euphorbiaceae / Q000737:chemistry*; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D012110:Reserpine / Q000008:administration & dosage; D013312:Stress, Physiological; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D010936:Plant Extracts; D000431:Ethanol; D012110:Reserpine
keywords: 5-HT(1B) receptor; Alchornea cordifolia; Depression; Forced swimming test; Parachlorophenylalanine; α-adrenoceptor