Metabolic and Behavioral Effects of Serotonergic Antidepressants in Rats Exposed to Swim Endurance Stress


  • Mehnaz Gitay University of Karachi, Karachi-75270, Pakistan
  • Samina Bano University of Karachi, Karachi-75270, Pakistan



 Swim endurance test, lipid profile, glycemic homeostasis, sertraline, tianeptine.


Metabolic syndrome (MS) is a collection of risk factors for coronary artery disease and type 2 diabetes. Prevalence of the MS in patients with depression is high and use of antidepressants also exert variable effects on constituent elements of the MS. Metabolic and behavioral effects of chronic serotonergic antidepressants treatment in rats subjected to swim endurance test (SET) were investigated. The Albino Wistar rats were divided into 2 groups vehicle (n=12) and drug (n=12). Each group was further divided into unstressed and stressed. Tianeptine (20 mg/kg), and sertraline (30 mg/kg), was administered orally for 28 days. Results showed that tianeptine and sertraline treatment correspondingly increase rat swimming time in SET. Swim stress raised circulating glucose, non-esterified free fatty acids (NEFFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and corticosterone levels with no effects on triglycerides (TGs). Drug alone administration showed that serum glucose levels were decreased by sertraline but not by tianeptine. Lipid levels were raised by both the drugs without effecting TGs. When drug treated stressed group was compared with the stressed controls, showed that tianeptine increases total cholesterol and LDL whereas TGs were decreased with no change on glucose levels. However sertraline treatment decreased the circulating glucose levels while the lipid profile remained unchanged. Corticosterone levels were increased by both the drugs. In conclusion, both the drugs may contribute potentially to the development of MS.It is suggested that antidepressant therapy should include routine surveillance for clinical and/or biochemical evidence suggestive of the metabolic syndrome.


Hoffman BB. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonist. In: Goodman and Gilman’s the pharmacological Basis of therapeutics (Eds. Hardman JG, Limbird LE and Gilman AG) 10th ed. McGraw-Hill, New York 2001; pp. 235-238.

Subarnas A, Tadano T, Nakahata N, Arai Y, Kinemuchi H, Oshima Y, et al. A Possible mechanism of antidepressant activity of beta-amyrinpalmitate isolated from Lobelia inflata leaves in the forced swimming test. Life Sci 1993; 52: 289-296.

Anisman H, Zacharko RM. Multiple neurochemical and behavioural consequences of stressors: Implications for depression. In: Psychopharmacology of anxiolytics and antidepressants. Pergamon Press, New York 1991; pp. 57-82.

Bhattacharya K, Ghosal S. Experimental evaluation of the anti-stress activity of a herbal formulation, zetress. J Nat Remedies 2000; 1: 1-7.

McIntyre RS, Woldeyohannes HO, Soczynska JK, Miranda A, Lachowski A, Liauw SS, et al. The Rate of Metabolic Syndrome in Euthymic Canadian Individuals with Bipolar I/II Disorder. Adv Ther 2010; 27(11): 828-36.

Muldoon MF, Mackey RH, Korytkowski MT, Flory JD, Pollock BG, Manuck SB. The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers. J Clin Endocrinol Metab 2006; 91(2): 718-21.

Grimsley SR, Jann MW. Paroxetine, sertraline, and fluvoxamine: new selective serotonin reuptake inhibitors. Clin Pharm 1992; 1: 930-57.

Rodriguez de la Torre B, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H, et al. Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients. Ther Drug Monit 2001; 23: 435-40.

Pollock BG, Laghrissi-Thode F, Wagner WR. Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment. J Clin Psychopharmacol 2000; 20(2): 137-40.

Borsini F. Models for depression in drug screening and preclinical studies: Future directions. World J Pharmacol 2012; 1(1): 21-29.

Moura LP, Bertolini NO, Ghezzi AC, Bertucci DR, Bonfim MR, Serafim THS, et al. Glucose Homeostasis in Type 1 Diabetic Rats after Acute Physical Activity. J Exer Physiol (Online) 2011; 14(6): 8-19.

Debnath J, Prakash T, Karki R, Kotresha D, Sharma P. An Experimental Evaluation of Anti-stress Effects of Terminaliachebula. J Physiol Biomed Sci 2011; 24(2): 13-19.

Lakshmi BVS, Sudhakar M. Screening of Psidiumguajava Leaf Extracts for Antistress Activity in Different Experimental Animal Models. Pharmacognosy Res 2009; 1(6): 359-66.

Kannur DM, Hukkeri VI, Akki KS. Adaptogenic activity of Caesalpiniabonduc seed extracts in rats. J Ethnopharmacol 2006; 108: 327-31.

Nimbakar SR, Patki VP, Patki MP. Pharmacological evaluation of anti-stress and androgenic activity of polyherbal formulation “A.P-3000”-containing Panaxginseng. Indian Drugs 2001; 38: 27-39.

Van Reedt Dortland AK, Giltay EJ, van Veen T, Zitman FG, Penninx BW. Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use. Acta Psychiatr Scand 2010; 122: 30-9.

Raeder MB, Fernø J, Vik-Mo AO, Steen VM. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects? Mol Cell Biochem 2006; 289(1-2): 167-73. Epub

Mikac Devic D, Stankovic H, Boskovic K. A method for determination of free fatty acids in serum. Clin Chim Acta 1973; 45(1): 55-59.

Glick D, Voredlich D, Levine S. Flourimetric determination of corticosterone and cortisol in 0.02 and 0.05 mls of plasma or submiligrams of adrenal tissue. Endocrinology 1964; 74: 653-65.

Bano S, Gitay M, Ara I, Badawy AAB. Acute effects of serotonergic antidepressants on tryptophan metabolism and corticosterone levels in rats. Pak J Pharm Sci 2010; 23(3): 266-72.

Fernstrom JD, Wurtman RJ. Brain serotonin content. increase following ingestion of carbohydrate diet. Science 1971; 174: 1023-25.

Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20(24): 9104-10.

Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301(5634): 805-9.

Vaidya VA, Duman RS. Depression--emerging insights from neurobiology. Br Med Bull 2001; 57: 61-79.

Holsboer F. Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord 2001; 62(1-2): 77-91.

Kivimäki M, Batty GD, Jokela M, Ebmeier KP, Vahtera J, Virtanen M, et al. Antidepressant Medication Use and Risk of Hyperglycemia and Diabetes Mellitus—A Noncausal Association? Biol Psychiatry 2011; 70(10): 978-84.

Hummel J, Westphal S, Weber-Hamann B, Gilles M, Lederbogen F, Angermeier T, et al. Serum lipoproteins improve after successful pharmacologic antidepressant treatment: a randomized open-label prospective trial. J Clin Psychiatry 2011; 72(7): 885-91.

Bailey D, Le Mellédo JM. Effects of serotonin reuptake inhibitors oncholesterol levels in patients with panic disorder. J Clin Psychopharmacol 2003; 23: 317-19.

Le Melledo JM, Mailo K, Lara N, Abadia MC, Gil L, Van Ameringen M, et al. Paroxetine-induced increase in LDL cholesterol levels. J Psychopharmacol 2009; 23(7): 826-30.

Sauer W, Berlin J, Kimmel SE. Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 2000; 108: 32-36.

Colotto M, Vinci F, Vo Hong N, Raimo O, Castle A, Carnovale A, et al. Effect of treatment with selective serotonin reuptake inhibitors on the lipid profile: state of the art. La Clinica Terapeutica 2012; 163(1): e41-45.

Teitelbaum M. Severe and Moderate Hypertriglyceridemia Secondary to Citalopram and Fluoxetine. Psychosomatics 2000; 41: 448-49.

Wei F, Crain AL, Whitebird RR, Godlevsky OV, O'Connor PJ. Effects of paroxetine and sertraline on low-density lipoprotein cholesterol: an observational cohort study. CNS Drugs 2009; 23(10): 857-65.

Webhofer C, Gormanns P, Tolstikov V, Zieglgänsberger W, Sillaber I, Holsboer F, et al. Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation. Transl Psychiatry 2011; 1(12): e58.

Gomez R, Huber J, Lhullier F, Barros HMT. Plasma insulin levels are increased by sertraline in rats under oral glucose overload. Braz J Med Biol Res 2001; 34(12): 1569-72.

Paulmann N, Grohmann M, Voigt JP, Bert B, Vowinckel J, Bader M, et al. Intracellular Serotonin Modulates Insulin Secretion from Pancreatic ?-Cells by Protein Serotonylation. PLoS Biol 2009; 7(10): e1000229.

Kesim M, Tiryaki A, Kadioglu M, Muci E, Kalyoncu NI, Yaris E. The effects of sertraline on blood lipids, glucose, insulin and HBA1C levels: A prospective clinical trial on depressive patients. J Res Med Sci 2011; 16(12): 1525-31.

Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Ann Rev Med 1998; 49: 235-61.




How to Cite

Mehnaz Gitay, & Samina Bano. (2013). Metabolic and Behavioral Effects of Serotonergic Antidepressants in Rats Exposed to Swim Endurance Stress. Journal of Basic & Applied Sciences, 9, 269–275.