Antidepressant activity of Simvastatin in behavioral  models of depression in rats

Archit Patke; Rakhi Tripathi; Vinay Govind Patke; Dipesh Sonawane; Nirmala Rege

doi:10.18203/2320-6012.ijrms20150248

Authors

Archit Patke Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai 400 052, Maharashtra
Rakhi Tripathi Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai 400 052, Maharashtra
Vinay Govind Patke Department of Biochemistry, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai 400 052, Maharashtra
Dipesh Sonawane Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai 400 052, Maharashtra
Nirmala Rege Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai 400 052, Maharashtra

DOI:

https://doi.org/10.18203/2320-6012.ijrms20150248

Keywords:

Simvastatin, Antidepressant, Fluoxetine, Forced swim test

Abstract

Background: There is evidence, that statins can augment the antidepressant effects of fluoxetine in rats. Hence
the present experimental study was designed to evaluate the effect of Simvastatin on duration of immobility in
acute forced swim test (Acute FST) and Chronic forced swim test (Chronic FST), as models of behavioral despair in rats.

Methods: In acute FST and Chronic FST models, effects of simvastatin (Smv) and fluoxetine (Flx) per se and in combination, on immobility of rats were compared. Open field test was performed to discriminate between the general behavioral stimulation and antidepressant effect of study drugs.

Results: In Acute FST, duration of immobility decreased (171.33 ± 6.15 sec) non-significantly in simvastatin group, & decreased significantly in the groups of rats which received fluoxetine alone (161.33 ± 8.68, P < 0.01) or in combination with simvastatin (167.66 ± 7.71 sec, P < 0.001). The 3 treatment groups did not differ from each other. In chronic FST duration of immobility lowered significantly in both, the fluoxetine treated group (147.66 ± 8.73) and the combination treated group (130.5 ± 5.68 sec) with significant fall in the combination group (P < 0.001) compared to the individual therapy groups.

Conclusions: Lowering cholesterol levels with statins not only reduces risks for cardiovascular events, but also affect serotonergic neurotransmission, leading to clinical efficacy of standard antidepressants. Simvastatin can augment the antidepressant effects of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.

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References

Enas EA, Senthilkumar. Coronary artery disease in Asian Indians: an update and review Internet Cardiol. 2001; 1.

Mathur KS. Environmental factors in coronary heart disease. Circulation. 1960;21:684-9.

Gupta R, Gupta VP, Ahluwalia NS. Educational status, coronary heart disease and coronary risk factor prevalence in a rural population in India. BMJ. 1994;307:1332–6.

Kutty VR, Balakrishnan KG, Jayasree AK, Thomas J. Prevalence of coronary heart disease In the rural population of Thiruvananthapuram district, Kerala, India. Int. 1993;39(1):59-70.

Van de Laak MF, van der Graaf Y, Banga JD, Simons PC, Algra A, Prevalence and treatment of hypercholesterolemia in patients with manifest vascular disease according to practice guidelines of the current cholesterol consensus) Ned Tijdschr Geneeskd. 2000;144(15):706-9.

Peter A Shapiro, Depression in Coronary Artery Disease: Does treatment help? Cleveland Clinic J Med. 2008;75:2.

Gayetot D, Ansseau M, Triffaux JM. When depression does not end. Resistant Depression: Recent Clinical and Therapeutic. Rev Med Liege. 2007;62(2):103-11.

Annu Rev Pharmacol Toxicol. 2005;45:89-118.

Renshaw PF, et al. Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats. Pharmacol Biochem Behav. 2009;92(1):88 – 92.

Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioral despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol. 1978;47:379–91.

Vogel H. Drug Discovery and Evaluation of Pharmacological Assay, 2nd edition 2002; 391-2.

Devadoss T, Pandey D, Mahesh R, Yadav S. Effect of acute and chronic treatment with a novel 5-HT3 receptor antagonist, in animal models of depression. Pharmacol Rep. 2010;62(2):245–57.

Dhingra D, Sharma A. Evaluation of antidepressant like activity of glycyrrhizinin mice. Indian J Pharmacol. 2005;37(6):390-94.

Miller BH, Schultz LE, Gulati A. Genetic regulation of behavioral responses to fluoxetine. Neuropsychopharmacology. 2010; 1-11.

Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996;19(2):179-200.

Renshaw PF, et al. Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats. Pharmacology Biochemistry and Behaviour. 2009;92(1):88–92.

Fergusson JA. SSRI Antidepressant Medications: Adverse Effects and Tolerability, Prim Care Companion J Clin Psychiatry. 2001;3(1):22-7.