DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20180100

The effect of docosahexaenoic acid (DHA) supplementation on experimental depression in mice

Tulika Singhal, Saroj Kothari

Abstract


Background: Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. Many drugs which are available as effective antidepressants produce various side effects like sedation weight gain postural hypotension etc., so there is need to develop novel compounds with minimized side effects. Hence this study was aimed to investigate the antidepressant activity of DHA, an omega-3 polyunsaturated fatty acid in albino mice.

Methods: Animals were divided into four groups, consisting six mice in each group. Out of these, group I served as control (2% gum acacia), group II and III received test drug in two different doses 200mg/kg and 300mg/kg respectively and group IV received fluoxetine (20mg/kg) as standard drug. To determine the antidepressant-like activity, we used forced swim test and tail suspension test in mice. These methods are based on the observation that a mouse show alternating agitation and immobility; the immobility is indicative of a state of depression.

Results: DHA produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control in both FST and TST. (P˂0.05) The efficacy of DHA at dose of 300 mg/kg was comparable with that of fluoxetine. DHA at 200mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. (P˂0.05).

Conclusions: The result specifies that compared to two doses of DHA (200mg/kg and 300mg/kg), higher dose of DHA found as an effective dose for treating depression produced due to stress.


Keywords


Docosahexaenoic acid, Forced swim test, Fluoxetine, Tail suspension test

Full Text:

PDF

References


O’Donnell J, Shelton R. Drug Therapy of Depression and Anxiety Disorders In: Brunton LB, Lazo JS, Parker KL, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. New York, NY: McGraw-Hill; 2005:397-415.

Shoeb A, Chowta M, Pallempati G, Rai A, Singh A. Evaluation of antidepressant activity of vanillin in mice. Indian J Pharmacol. 2013 Mar;45(2):141.

Matreja PS, Badyal DK, Deswal RS, Sharma A. Efficacy and safety of add on low-dose mirtazapine in depression. Indian J Pharmacol. 2012 Mar;44(2):173.

Whooley MA, Simon GE. Managing depression in medical outpatients. N Engl J Med 2000;343:1942‑50.

Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacological Research. 1999 Sep 1;40(3):211-25.

Bradbury J. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients. 2011 May 10;3(5):529-54.

Guesnet P, Alessandri JM. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS)- Implications for dietary recommendations. Biochimie. 2011 Jan 31;93(1):7-12.

De la Presa Owens S, Innis SM. Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a linoleic and α-linolenic acid deficient diet in formula-fed piglets. J Nutr. 1999 Nov 1;129(11):2088-93.

Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G. α‐Linolenic Acid Dietary Deficiency Alters Age‐Related Changes of Dopaminergic and Serotoninergic Neurotransmission in the Rat Frontal Cortex. J Neurochem. 1996 Apr 1;66(4):1582-91.

Jenner PG. Antidepressants: Neurochemical, Behavioral and Clinical Perspectives. J Neurol Neurosur, Ps. 1982 Jun;45(6):574.

Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM. Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Be. 1997 Jan 31;56(1):131-7.

Butterweck V, Nishibe S, Sasaki T, Uchida M. Antidepressant Effects of Apocynum venetum Leaves in a Forced Swimming Test. Biol. Pharm. Bull. 2001;24(7):848-51.

Detke MJ, Lucki I. Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth. Beha Brain Res. 1995 Dec 15;73(1):43-6.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 1985 Mar 1;85(3):367-70.

Hamilton M. A rating scale for depression. J Neurol Neurosurg Ps. 1960;23:56‑62.

Kumari J, Yadav S, Sharma V. Dcosahexaenoic Acid: wonder dietary supplement. International J Ther Appl. 2012;(3):25-31.

Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, Endo Y, Perez E, de Lera AR, et al, Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol. Psychiatry. 2011;69:788e-794e.

Jiang LH, Liang QY, Shi Y. Pure docosahexaenoic acid can improve depression behaviors and affect HPA axis in mice. Cellulose. 2012;50:50.

Zhang L, Zhu Z, Tan Z, Luo H, Hu X, Li Y. Docosahexaenoic acid induces glial cell-line derived neurotrophic factor release in C6 glioma cells: Implications of antidepressant effects for docosahexaenoic acid. Biochem Bio Res Co. 2017 Aug 7.

Smith DJ, Sarris J, Dowling N, O'Connor M, Ng CH. Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial. Nutr Neurosci. 2017 Feb 22:1-5.