Association between HMG CoA reductase inhibitors and anxiety:an experimental study using elevated plus maze and light dark arena behavioural models


  • Anupama M. Gudadappanavar Department of Pharmacology, J. N. Medical College, KLE University, Belgaum, Karnataka
  • Prashant R. Hombal Department of General Surgery, J. N. Medical College, KLE University, Belgaum, Karnataka



Simvastatin, Atorvastatin, Lovastatin, Anxiety, Cholesterol, Serotonin


Background: Aims: To investigate the effect of HMG CoA reductase inhibitors on behavioural models of anxiety in male swiss mice using Elevated plus maze test and light-dark arena test.

Methods: It was an experimental study, carried out in department of Pharmacology, J. N. Medical College, KLE University, Belgaum. The in vivo behavioural activity of simvastatin, lovastatin, atorvastatin was studied using EPM and light-dark arena test. The mice received the drugs as per their weight and subjected for experimentation. Group mean time spent and number of entries into open arm in EPM test and group mean number of entries and time spent in the light area was calculated in treated and control groups for comparison. Statistical analysis was done using ANOVA followed by Bonferroni’s multiple comparison test (P<0.05).

Results: Going through the results of this study an evidence for the association between lowered serum cholesterol and symptoms of anxiety can be seen as statins used in the present study failed to show significant anxiolytic effect when compared to standard but in turn showed even more less activity when compared to control, indicating anxiogenic behavior.

Conclusions: Our findings support the evidence of the negative effects of statins on psychological outcomes.  It's generally understood that having low cholesterol is a good health sign, combined with other factors; it could actually put a person at risk by causing anxiety and stress. Further research comprising a greater number of studies is required to confirm the effects of this agent on psychological outcomes.  



Stahl SM. Essential psychopharmacology. In: Stahl SM, eds. A Book. 2nd ed. New Delhi: Foundation Books, Cambridge University Press; 2000.

Tandon V, Bano G, Khajuria V, Parihar A, Gupta S. Pleiotropic effects of statins. Indian J Pharmacol. 2005;37(12):75-85.

Anil Kumar, Aditi Vashist, Puneet Kumar, Harikesh Kalonia, Jitendriya Mishra. Protective effect of HMG CoA reductase inhibitors against running wheel activity induced fatigue, anxiety like behavior, oxidative stress and mitochondrial dysfunction in mice. Pharmacol Rep. 2012;64:1326-36.

Fatma S. Kilic, Yasemin Ozatik, Bilgin Kaygisiz, Canan Baydemir, Kevser Erol. Acute antidepressant and anxiolytic effects of simvastatin and its mechanisms in rats. Neurosciences. 2012;17(1):39-43.

Brunton LL, Laso JS, Parker KL, Goodman Gilman A. The pharmacological basis of therapeutics. In: Brunton LL, Laso JS, Parker KL, Goodman Gilman A, eds. A Book. 11th ed. New York: McGraw Hill; 2001.

Gudadappanavar Anupama M, Hiremath Shrishail V, Torgal Shashikant. Evaluation of antidepressant activity of simvastatin lovastatin and atorvastatin in male swiss mice - an experimental study. Int J Drug Dev Res. 2013 Apr-Jun;5(2):99-102.

Gosh MN. Fundamentals of experimental pharmacology. In: Gosh MN, eds. A Book. 4th ed. Kolkota: Hilton And Company; 2005.

Vogel GH, Vogel WH. Drug discovery and evaluation, pharmacological assays. In: Vogel GH, Vogel WH, eds. A Book. 2nd ed. New York: Springer-Verlag Berlin Heidelberg; 2002.

Kulkarni SK. Handbook of experimental pharmacology. In: Kulkarni SK, eds. A Book. 2nd ed. Delhi: Vallabh Prakashan; 1993. New York: Springer Verlag Berlin Heidelberg; 2002.

Veena N, Patil PA. Antidepressant activity of fosinopril, ramipril, and losartan, but not of lisinopril in depressive paradigms of albino rats and mice. Indian J Experiment Biol. 2008;46:180-4.

Schneider P, Ho YJ, Spanagel R, Pawlak CR. A novel elevated plus-maze procedure to avoid the one-trial tolerance problem. Front Behav Neurosci. 2011;5:43.

Andreatini R, Bacellar LFS. The relationship between anxiety and depression in animal models: a study using the forced swimming test and elevated plus-maze. Braz J Med Biol Res. 1999;32:1121-6.

Jaya Mary Thomas, Joyamma Varkey, Bibin Baby Augustine. Association between serum cholesterol, brain serotonin, and anxiety: a study in simvastatin administered experimental animals. Int J Nutr Pharmacol Neurol Diss. 2014 Jan-Mar;4(1):69-73.

George I. Papakostas, Dost O¨ngu¨r, Dan V. Iosifescu, David Mischoulon, Maurizio Fava. Cholesterol in mood and anxiety disorders: review of the literature and new hypotheses. Eur Neuropsychopharmacol. 2004;14:135-42.

Sjogren B, Hambline MW, Svenningsson P. Cholesterol depletion reduces serotonin binding and signalling via human 5HT(7(a)) receptors, Eur J Pharmacol. 2006 Dec;552(1-3):1-10.

Long-Jun Wu, Susan S. Kim, Min Zhuo. Molecular targets of anxiety: from membrane to nucleus. Neurochem Res. 2008;33:1925-32.




How to Cite

Gudadappanavar, A. M., & Hombal, P. R. (2017). Association between HMG CoA reductase inhibitors and anxiety:an experimental study using elevated plus maze and light dark arena behavioural models. International Journal of Research in Medical Sciences, 3(6), 1329–1335.



Original Research Articles