title: Acute antidepressant and anxiolytic effects of simvastatin and its mechanisms in rats.
abstract: OBJECTIVE
  The aim of this study is to investigate the antidepressant and anxiolytic effects of simvastatin in rats.
  
  
  METHODS
  Sixty-four male adult (8-9 weeks old) Sprague-Dawley rats (200-250 g) were used. The forced swimming test and the elevated plus maze test were used for testing the antidepressant and anxiolytic effects. Eight groups were formed: control (saline), simvastatin 10, 30, and 50 mg/kg, amitriptyline 10 mg/kg, sertraline 5 mg/kg, simvastatin 30 mg/kg+amitriptyline 10 mg/kg, and simvastatin 30 mg/kg+sertraline 5mg/kg combinations. The study was conducted at the Animal Experiment Laboratories, Department of Pharmacology, Eskisehir Osmangazi University Medical School, Eskisehir, Turkey from March to May 2010.
  
  
  RESULTS
  The immobility periods were significantly reduced by all doses of simvastatin. Simvastatin 10 and 30 mg/kg but not 50 mg/kg increased time spent in the open arm. A single dose of amitriptyline 10 mg/kg showed significant antidepressant and anxiolytic effects. Sertraline 5 mg/kg showed significant antidepressant, but not anxiolytic effects. There was no change in the antidepressant and anxiolytic effects of simvastatin when combined with amitriptyline. A potentialization in antidepressant effect, and a decrease in anxiolytic effect of simvastatin were observed in combinations of simvastatin and sertraline.
  
  
  CONCLUSIONS
  Simvastatin presents significant antidepressant and anxiolytic effects in rats similar to selective serotonin reuptake inhibitors, and interactions between the effects of simvastatin on indoleamine 2,3-dioxygenase enzymes, N-methyl-D-aspartic acid receptor blockade, and dopaminergic functions possibly mediate its antidepressant and anxiolytic effects.
authors.affiliation: Department of Pharmacology, Medical School, Eskisehir Osmangazi University, Meselik Kampusu, Eskisehir, Turkey. fskilic@ogu.edu.tr
authors.forename: Fatma S
authors.initials: FS
authors.lastname: Kilic
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Ozatik
authors.forename: Bilgin
authors.initials: B
authors.lastname: Kaygisiz
authors.forename: Canan
authors.initials: C
authors.lastname: Baydemir
authors.forename: Kevser
authors.initials: K
authors.lastname: Erol
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000639:Amitriptyline; D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D019821:Simvastatin