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Drug Res (Stuttg) 2016; 66(05): 235-245
DOI: 10.1055/s-0035-1565174
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Antidepressant Effect of Cnestis ferruginea Vahl ex DC (Connaraceae): Involvement of Cholinergic, Monoaminergic and L-arginine-nitric Oxide Pathways

T. E. Owope
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria
,
I. O. Ishola
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria
,
M. O. Akinleye
2   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, Idi-Araba, Lagos, Nigeria
,
R. Oyebade
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria
,
O. O. Adeyemi
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Science, College of Medicine, University of Lagos, Lagos, Nigeria
› Author Affiliations
Further Information

Publication History

received 08 May 2015

accepted 26 October 2015

Publication Date:
20 January 2016 (online)

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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 NG-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.

Conclusion: 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.

Key words

adrenoceptors - forced swim test - 5-HT2B receptor - 5-HT6 receptor - L-arginine-nitric oxide
 

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