A STUDY ON THE EFFECTS OF AGOMELATINE ON FOOD INTAKE AND BODY WEIGHT IN RESTRAINT STRESS MODEL IN ADULT SWISS ALBINO MICE
Â Objectives: Agomelatine is a novel melatonin (MT) receptor agonist at MT 1 and 2, serotonin receptor antagonist and an effective chronobiotic agent. The study was designed to evaluate the effects of agomelatine on body weight and food intake in restraint stress model in adult Swiss albino mice.
Methods: After the approval of Institutional Animal Ethics Committee, 40 male Swiss albino mice were randomly divided into four groups of 10 animals each; two were treatment groups which received 25 mg/kg (low dose) agomelatine, 50 mg/kg (high dose) agomelatine, standard group given trazodone and the control group administered the vehicle (1% hydroxyethyl cellulose [HEC]) intraperitoneally for the last 14 days in the 3 weeks study period. Chronic restraint stress was given for 4 hrs per day for all groups starting from day 0 to 21.
Results: Using paired t-test, both 12 hrs (p=0.011) and 24 hrs (p<0.001) food intake in the high dose agomelatine group were significantly increased. Between groups using ANOVA test showed a statistically significant increase in food intake for this group when compared to the control group. Unlike the low dose agomelatine group (p=0.205), the mean body weight in the group treated with high dose agomelatine revealed a statistically significant rise compared to that of the control (p=0.001) in ANOVA test.
Conclusion: High dose agomelatine was effective in antagonizing the body weight lowering effect of restraint stress in addition to amelioration of reduced food intake. The study has potentially brought out the additional therapeutic benefit of agomelatine in improving the altered feeding and body weight changes when used in the treatment of the depression.
2. Barua A, Ghosh MK, Kar N, Basilio MA. Prevalence of depressive disorders in the elderly. Ann Saudi Med 2011;31:620-4.
3. Pilania M, Bairwa M, Khurana H, Kumar N. Prevalence and predictors of depression in community-dwelling elderly in rural Haryana, India. Indian J Community Med 2017;42(1):13-8.
4. Worboys M. The Hamilton rating scale for depression: The making of a â€˜gold standardâ€™ and the unmaking of a chronic illness, 1960-1980. Chronic Illn 2013;9(3):202-19.
5. de Wit LM, van Straten A, van Herten M, Penninx BW, Cuijpers P. Depression and body mass index, a u-shaped association. BMC Public Health 2009;9:14.
6. Guaiana G, Gupta S, Chiodo D, Davies SJ, Haederle K, Koesters M. Agomelatine versus other antidepressive agents for major depression. Cochrane Database Syst Rev 2013;12:CD008851.
7. Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, Popovska-Gorevski M, Dubocovich ML. MT1 and MT2 melatonin receptors: A therapeutic perspective. Annu Rev Pharmacol Toxicol 2016;56:361-83.
8. Reagan LP, Reznikov LR, Evans AN, Gabriel C, MocaÃ«r E, Fadel JR. The antidepressant agomelatine inhibits stress-mediated changes in amino acid efflux in the rat hippocampus and amygdala. Brain Res 2012;1466:91-8.
9. Budni J, Zomkowski AD, Engel D, Santos DB, dos Santos AA, Moretti M, et al. Folic acid prevents depressive-like behavior and hippocampal antioxidant imbalance induced by restraint stress in mice. Exp Neurol 2013;240:112-21.
10. Jiang SZ, Eiden LE. Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACA Pergic neurotransmission in the mouse. Stress 2016;19(4):374-82.
11. Arafat M. Approaches to achieve an oral controlled release drug delivery system using polymers: A recent review. Int J Pharm Pharm Sci 2015;7(7):16-21.
12. Shanmugapriya S, Senthurselvi R, Bhuvaneswari K. A study comparing the anorectic activity of hot and cold aqueous extracts of Dolichos biflorus Linn. Seeds in freely feeding rats. Int J Pharm Pharm 2016;8(7):336-9.
13. Ladurelle N, Gabriel C, Viggiano A, MocaÃ«r E, Baulieu EE, Bianchi M. Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC. Psychopharmacology (Berl) 2012;221(3):493-509.
14. Conboy L, Tanrikut C, Zoladz PR, Campbell AM, Park CR, Gabriel C, et al. The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats. Int J Neuropsychopharmacol 2009;12(3):329-41.
15. de Bodinat C, Guardiola-Lemaitre B, MocaÃ«r E, Renard P, MuÃ±oz C, Millan MJ. Agomelatine, the first melatonergic antidepressant: Discovery, characterization and development. Nat Rev Drug Discov 2010;9(8):628-42.
16. Haque Z, Akbar N, Yasmin F, Haleem MA, Haleem DJ. Inhibition of immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion by injected leptin in rats. Stress 2013;16(3):353-62.
17. Jeong JY, Lee DH, Kang SS. Effects of chronic restraint stress on body weight, food intake, and hypothalamic gene expressions in mice. Endocrinol Metab (Seoul) 2013;28(4):288-96.
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