title: Antidepressant Effect of Cnestis ferruginea Vahl ex DC (Connaraceae): Involvement of Cholinergic, Monoaminergic and L-arginine-nitric Oxide Pathways.
abstract: BACKGROUND
  We have previously reported antidepressant effect of Cnestis ferruginea (CF) in behavioral models of depression. Due to the promise shown by this extract, this study was carried out to investigate the contribution of monoaminergic, cholinergic and nitrergic systems to the antidepressant-like effect elicited by CF.
  
  
  METHODS
  Male albino mice were pretreated with monoaminergic or cholinergic receptor antagonists, L-arginine or N(G)-nitro-L-arginine (nitric oxide synthase inhibitor) (at doses reported to block the in vivo effect of the agonists), 15 min before oral administration of CF (100 mg/kg), 1 h later, the forced swim test (FST) in mice was carried out.
  
  
  RESULTS
  CF treatment produced significant changes in the duration of swimming (F(5,42)=9.86, P<0.001), climbing behaviour (F(5,42)=4.51, P=0.004) and mean time spent immobile (F(5,42)=11.55, P<0.001) vs. vehicle-treated control. Co-administration of CF with fluoxetine or imipramine potentiated their effect. However, pretreatment of mice with reserpine (F(1,16)=119.20, P<0.001), prazosin (F(1,16)=68.98, P<0.001), sulpiride (F(1,16)=15.46, P<0.01), RS 127445 ((F(1,20)=8.22, P<0.01), SB 399885 ((F(1,20)=38.44, P<0.001), atropine (F(1,16)=53.77, P<0.001), or L-arginine (nitric oxide precursor) (F(1,16)=10.35, P<0.01) prevented CF-induced antidepressant-like effect in mice. In addition, pretreatment of mice with L-NNA (10 mg/kg) augmented the effect of CF.
  
  
  CONCLUSIONS
  C. ferruginea exerts its antidepressant-like action through interaction with α-adrenoceptor, dopamine D2, 5-HT2B, 5-HT6 and muscarinic cholinergi1c receptors as well as L-arginine-nitric oxide systems. C. ferruginea could be used as adjuvant with conventional antidepressants in the treatment of major depressive disorder.
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: T E
authors.initials: TE
authors.lastname: Owope
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: I O
authors.initials: IO
authors.lastname: Ishola
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, Idi-Araba, Lagos, Nigeria.
authors.forename: M O
authors.initials: MO
authors.lastname: Akinleye
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: R
authors.initials: R
authors.lastname: Oyebade
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: O O
authors.initials: OO
authors.lastname: Adeyemi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D031961:Connaraceae / Q000737:chemistry*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D016488:Medicine, African Traditional / Q000379:methods*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009549:Nigeria; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D018680:Cholinergic Antagonists; D010936:Plant Extracts; D011950:Receptors, Cholinergic; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase