title: Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats.
abstract: BACKGROUND
  Cholesterol may have a role in the pathophysiology of depression. Lowering cholesterol levels with statins reduces risks for cardiovascular events, and there is clinical evidence that statins exert neuroprotective properties not fully explained by their effects on serum cholesterol levels. Altered cholesterol levels can affect serotonergic neurotransmission, which might be involved in the clinical efficacy of standard antidepressants.
  
  
  METHODS
  We examined interactions between a statin (lovastatin) and a selective serotonin reuptake inhibitor (fluoxetine) using the forced swim test (FST) in rats, a behavioral assay that identifies treatments with antidepressant effects in humans. Specifically, we determined if the addition of lovastatin to the diet would increase the efficacy of a subeffective dose of fluoxetine.
  
  
  RESULTS
  Rats maintained on a lovastatin-enriched diet for 30 days were more sensitive to the antidepressant-like effects of a low (subthreshold) dose of fluoxetine. The behavior of rats treated with this combination resembled that normally seen with higher doses of fluoxetine. No effects were observed in rats maintained on a lovastatin-enriched diet for 3 days.
  
  
  CONCLUSIONS
  Lovastatin can augment the antidepressant-like effects of a low dose of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Belmont, MA 02478, USA. perry.renshaw@hsc.utah.edu
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: Aram
authors.initials: A
authors.lastname: Parsegian
authors.forename: C Kevin
authors.initials: CK
authors.lastname: Yang
authors.forename: Aileen
authors.initials: A
authors.lastname: Novero
authors.forename: Sujung J
authors.initials: SJ
authors.lastname: Yoon
authors.forename: In Kyoon
authors.initials: IK
authors.lastname: Lyoo
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004032:Diet; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D005473:Fluoxetine; D008148:Lovastatin