Antidepressant and Anxiolytic Effects of the Methanol Root Extract of Capparis thonningii: Involvement of Monoaminergic, Cholinergic and GABAergic Systems

I. O. Ishola; S. O. Olayemi; O. K. Yemitan; E. A. Umeh

doi:10.1055/s-0034-1376963

Drug Research, Table of Contents

Drug Res (Stuttg) 2015; 65(04): 205-213
DOI: 10.1055/s-0034-1376963

Original Article

Antidepressant and Anxiolytic Effects of the Methanol Root Extract of Capparis thonningii: Involvement of Monoaminergic, Cholinergic and GABAergic Systems

Authors

I. O. Ishola

¹Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria
S. O. Olayemi

¹Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria
O. K. Yemitan

²Department of Pharmacology, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, Lagos State, Nigeria
E. A. Umeh

¹Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria

Abstract

Background: Capparis thonningii Schum. (Capparaceae) is used in traditional African Medicine for the treatment of mood disorders.

Objective: The study investigates antidepressant and anxiolytic activities of methanol root extract of C. thonningii (CT).

Methods: CT (25–100 mg/kg, p. o.) was administered 1 h before behavioral studies were carried out in mice. Antidepressant effect was investigated using the forced swimming test (FST) and tail suspension test (TST). The anxiolytic effect was evaluated using the elevated-plus maze test (EPM), hole-board test (HBT), and light-dark test.

Results: CT (25 and 50 mg/kg) increased swimming activity (P<0.05) by 92.73% and attenuated immobility time by 35.72%, similar to anti-immobility effect of imipramine (33.87%) in FST. In addition, CT (50 mg/kg) significantly (P<0.01) reduced immobility time by 30.24% in TST. However, the antidepressant-like effect elicited by CT was reversed by metergoline, cyproheptadine, and sulpiride (40.81, 45.93, and 48.52%, respectively) pretreatment but prazosin, and yohimbine failed to reverse this antidepressant-like effect. Similar to diazepam, CT (25 mg/kg) increased duration of open arms exploration (P<0.05) by 43.73% in EPM, number of head-dips (HBT) (90.32%), and time spent in the light compartment by 45.77% in light/dark test indicating anxiolytic-like effect. The anxiolytic-like effect of CT was reversed by flumazenil pretreatment.

Conclusion: The findings from this study suggest antidepressant-like effect of C. thonningii involving interaction with serotonergic (5-HT₂), dopaminergic (D₂), noradrenergic (α₁ and α₂), and muscarinic cholinergic systems; and anxiolytic effect through an interaction with GABA_A benzodiazepine receptor.

Key words

α₂ adrenoceptor - benzodiazepine receptor - C. thonningii - forced swimming test - muscarinic cholinergic systems

Full Text

References

References
1 Zhang Z. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci 2004; 75: 1659-1699
2 Burkhill HM. The Useful Plants of West Tropical Africa. vol. 1. UK: White Friars Press; 1985
3 Ajaiyeoba EO, Sama W. Phytochemical and antimicrobial studies of C. thonningii and C. tormentosa . Pharmacog Mag 2006; 2: 118-122
4 Ishola IO, Adeyemi OO, Agbaje EO et al. Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory deficit in mice. Pharm Biol 2013; 51: 49-57
5 Spencer JPE. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Soc 2008; 67: 238-252
6 Dias GP, Cavegn N, Nix A et al. The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid Med Cell Longev 2012; 541971: 1-18
7 An L, Zhang YZ, Yu NJ et al. The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Prog Neuro-Psychopharmacol Biol Psychiatry 2008; 2: 1484-1490
8 Vignes M, Maurice T, Lanté F et al. Anxiolytic properties of green tea polyphenol (-)-epigallocatechin gallate (EGCG). Brain Res 2006; 1110: 102-115
9 Zhu WL, Shi HS, Wei YM et al. Green tea polyphenols produce antidepressant-like effects in adult mice. Pharmacol Res 2012; 65: 74-80
10 Edeoga HO, Okwu DE, Mbaebie BO. Phytochemical constituents of some Nigerian medicinal plants. Afr J Biotechnol 2005; 4: 685-688
11 Ishola IO, Akindele JA, Adeyemi OO. Sub-chronic toxicity (90 days) study of the methanol root extract of Cnestis ferruginea . Pharm Biol 2012; 50: 994-1006
12 Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229: 327-336
13 Steru L, Chermat R, Thierry B et al. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacol 1985; 85: 367-370
14 Ulak G, Muttu O, Tanyen P et al. Involvement of serotonin receptor subtypes in the antidepressant-like effect of trim in the rat forced swimming test. Pharmacol Biochem Behav 2010; 95: 308-314
15 Stachowicz K, Chojnacka-Wójcik E, Kłak K et al. Anxiolytic-like effect of group IIImGlu receptor antagonist is serotonin-dependent. Neuropharmacol 2007; 52: 306-312
16 Gu L, Liu Y, Wang Y et al. Role for monoaminergic systems in the antidepressant-like effect of ethanol extracts from Hemerocallis citrina . J Ethnopharmacol 2012; 139: 780-787
17 Liebenberg N, Wegener G, Harvey BH et al. Investigating the role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism. Behav Brain Res 2010; 209: 137-141
18 Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacol 1987; 92: 180-185
19 Hogg S. A review of the validity and variability of the elevated plus maze as an animal model of anxiety. Pharmacol Biochem Behav 1996; 54: 21-30
20 Adeyemi OO, Yemitan OK, Taiwo AE. Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL. J Ethnopharmacol J 2006; 106: 312-316
21 Yemitan OK, Salahdeen HM. Neurosedative and muscle-relaxant activities of aqueous extract of Bryophyllum pinnatum . Fitoterapia 2005; 76: 187-193
22 Chatterjee M, Verma P, Maurya R et al. Evaluation of ethanol leaf extract of Ocimum sanctum in experimental models of anxiety and depression. Pharm Biol 2011; 49: 477-483
23 Nogueira E, Vassilieff VS. Hypnotic, anticonvulsant and muscle relaxant effects of Rubus brasiliensis. Involvement of GABA_A-system. J Ethnopharmacol 2000; 70: 275-280
24 Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 2005; 29: 571-625
25 Bourin M, Chenu F, Ripoll N et al. A proposal of decision tree to screen putative antidepressants using forced swim and tail suspension tests. Behav Brain Res 2005; 164: 266-269
26 Dekte MJ, Richell M, Lucki I. Active behaviors in the rat forced swim test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacol 1995; 121: 66-72
27 Cryan JF, Lucki I. Antidepressant-like behavioral effects mediated by 5- HT_2c receptors. J Pharmacol Exp Ther 2000; 295: 1120-1126
28 Cryan JF, Page ME, Lucki I. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swimming test. Eur J Pharmacol 2002; 436: 197-205
29 Frazer A. Norepinephrine involvement in antidepressant action. J Clin Psychiatry 2000; 61: 25-30
30 Nutt DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 2006; 67: 3-8
31 Danysz W, Kostowski W, Kozak W et al. On the role of noradrenergic neurotransmission in the action of desipramine and amitriptyline in animal models of depression. Pol J Pharmacol Pharm 1986; 38: 285-298
32 Masuda Y, Ohnuma S, Sugiyama T. Alpha 2-adrenoceptor activity induces the antidepressant-like glycolipid in mouse forced swimming. Methods Find Exp Clin Pharmacol 2001; 23: 19-21
33 Kreiss DS, Lucki I. Effects of acute and repeated administration of antidepressant drugs on extracellular levels of 5-hydroxytryptamine measured in vivo. J Pharmacol Exp Ther 1995; 274: 866-876
34 Binfaré RW, Rosa AO, Lobato KR et al. Ascorbic acid administration produces an antidepressant-like effect: Evidence for the involvement of monoaminergic neurotransmission. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 530-540
35 McLean A, Rubinsztein JS, Robbins TW et al. The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression. Psychopharmacol (Berl) 2004; 171: 286-297
36 Dagyte G, Den Boer JA, Trentani A. The cholinergic system and depression. Behav Brain Res 2011; 221: 574-582
37 Moreira EG, Nascimento N, Rogero JR et al. GABAergic benzodiazepine system is involved in the crotoxin-induced anxiogenic effect. Pharmacol Biochem Behav 2000; 65: 7-13
38 Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 1998; 350: 21-29
39 Young R, Johnson DN. A fully automated light/dark apparatus useful for comparing anxiolytic agents. Pharmacol Biochem Behav 1991; 40: 739-743
40 Xu Y, Ku B, Cui L et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor IA mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 2007; 1162: 9-18
41 Van Praag H, Lucero MJ, Yeo GW et al. Plant-derived flavanol(-) epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 2007; 27: 5869-5878
42 Messaoudi M, Bisson JF, Nejdi A et al. Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats. Nutri Neurosci 2008; 11: 269-276
43 Zhu WL, Shi HS, Wei YM et al. Green tea polyphenols produce antidepressant-like effects in adult mice. Pharmacol Res 2012; 65: 74-80