Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress

Pharmacol Biochem Behav. 2014 Sep:124:174-9. doi: 10.1016/j.pbb.2014.06.006. Epub 2014 Jun 12.

Abstract

Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4 weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.

Keywords: Antidepressant; Chronic mild stress; Forced swim test; Simvastatin; Sucrose preference test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Corticosterone / blood
  • Depression / drug therapy*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use*
  • Stress, Psychological*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Corticosterone