Evaluation of antidepressant activity of tramadol in mice: an experimental study
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20150017Keywords:
Antidepressant, Tramadol, FluoxetineAbstract
Background: In spite of availability of effective antidepressant drugs, depression continues to be a major problem. Hence, great interest is being taken in development of innovative antidepressants. Tramadol (TRM) is a centrally acting opioid agonist, which is clinically effective in the treatment of moderate to severe pain. By virtue of its action of inhibiting norepinephrine and serotonin uptake, it can function as an antidepressant like venlafaxine. Hence, this study was planned to evaluate antidepressant activity of TRM in comparison and in combination with fluoxetine (FLX) in albino mice.
Methods: TRM (20 and 40 mg) and FLX (20 mg) were administered i.p., alone and in combination once daily for acute (7 days) and chronic (14 days) period to Swiss albino mice of either sex. The immobility period of control and treated mice was recorded in forced swimming test (FST) and tail suspension test (TST). The open field test was also done for same period to test the locomotor activity in animal. The antidepressant effect of TRM was compared with FLX and normal saline treated group for acute and chronic study period.
Results: TRM (20 and 40 mg) treated group produced significant antidepressant effect alone and in combination with FLX (20 and 40 mg) as indicated by reduction in immobility period compared with control group in FST and TST. TRM and FLX treated groups did not show significant activity in open field test when compared with control group.
Conclusions: This study shows TRM has antidepressant activity in standard models of depression.
References
Murthy RS, Bertolote JM, Epping-Jordan J, Funk M, Prentice T, Saraceno B, et al. Public health approach to mental health. The World Health Report 2001 - Mental Health: new Understanding, New Hope. 1st Edition. France: WHO Graphics; 2001: 1-16.
Yu ZF, Kong LD, Chen Y. Antidepressant activity of aqueous extracts of Curcuma longa in mice. J Ethnopharmacol. 2002;83(1-2):161-5.
Rojas-Corrales MO, Gibert-Rahola J, Micó JA. Tramadol induces antidepressant-type effects in mice. Life Sci. 1998;63(12):PL175-80.
Driessen B, Reimann W, Giertz H. Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro. Br J Pharmacol. 1993;108(3):806-11.
Sevcik J, Nieber K, Driessen B, Illes P. Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones. Br J Pharmacol. 1993;110(1):169-76.
Kiayias JA, Vlachou ED, Lakka-Papadodima E. Venlafaxine HCl in the treatment of painful peripheral diabetic neuropathy. Diabetes Care. 2000;23(5):699.
Kishore RN, Anjaneyulu N, Ganesh MN, Sravya N, Abhinayani G, Pratyusha C. Evaluation of antidepressant activity of tramadol hydrochloride in mice model. World J Pharm Pharm Sci. 2012;1(4):1384-91.
Szkutnik-Fiedler D, Kus K, Balcerkiewicz M, Grzeskowiak E, Nowakowska E, Burda K, et al. Concomitant use of tramadol and venlafaxine - evaluation of antidepressant-like activity and other behavioral effects in rats. Pharmacol Rep. 2012;64(6):1350-8.
Chowta MN, Manjunath M, Gopalakrishna HN, Gokul P. Evaluation of role of noradrenergic system in the antidepressant activity of tramadol using tail suspension test in Albino mice. J Pharmacol Pharmacother. 2011;2(4):281-2.
Kalra BS, Tayal V, Chawla S. Antidepressant-like activity of tramadol in mice. Indian J Psychiatry. 2008;50(1):51-3.
Santosh P, Venugopl R, Nilakash AS, Kunjbihari S, Mangala L. Antidepressant activity of Passiflora foetida leaves in mice. Indian J Pharm Pharm Sci. 2011;3(1):112-5.
Markowitz JS, Patrick KS. Venlafaxine-tramadol similarities. Med Hypotheses. 1998;51(2):167-8.
Berrocoso E, Rojas-Corrales MO, Mico JA. Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice. Psychopharmacology (Berl). 2006;188(1):111-8.
Yalcin I, Coubard S, Bodard S, Chalon S, Belzung C. Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on the antidepressant-like action of tramadol in the unpredictable chronic mild stress in mice. Psychopharmacology (Berl). 2008;200(4):497-507.
Jesse CR, Wilhelm EA, Bortolatto CF, Nogueira CW. Evidence for the involvement of the noradrenergic system, dopaminergic and imidazoline receptors in the antidepressant-like effect of tramadol in mice. Pharmacol Biochem Behav. 2010;95(3):344-50.
Berrocoso E, Sánchez-Blázquez P, Garzón J, Mico JA. Opiates as antidepressants. Curr Pharm Des. 2009;15:1612-22.
Jesse CR, Bortolatto CF, Savegnago L, Rocha JB, Nogueira CW. Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(8):1838-43.
Faron-Górecka A, Kusmider M, Inan SY, Siwanowicz J, Dziedzicka-Wasylewska M. Effects of tramadol on alpha2-adrenergic receptors in the rat brain. Brain Res. 2004;1016(2):263-7.
Faron-Górecka A, Kusmider M, Inan SY, Siwanowicz J, Piwowarczyk T, Dziedzicka-Wasylewska M. Long-term exposure of rats to tramadol alters brain dopamine and alpha 1-adrenoceptor function that may be related to antidepressant potency. Eur J Pharmacol. 2004;501(1-3):103-10.
Aysegul Y, Ali SG, Lut T. Mechanism of actions of antidepressants: beyond the receptors. Bull Clin Psychopharmacol. 2002;12(4):194-200.
