Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats

Cited 29 time in Web of Science Cited 28 time in Scopus

Renshaw, Perry F.; Parsegian, Aram; Yang, C Kevin; Novero, Aileen; Yoon, Sujung J.; Lyoo, In Kyoon; Cohen, Bruce M; Carlezon, William A. Jr

Issue Date
Pharmacol Biochem Behav. 2009 ;92(1):88-92.
AnimalsAntidepressive Agents/*pharmacologyDepression/*drug therapy/psychologyDietDrug SynergismFluoxetine/*pharmacologyHydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacologyLovastatin/*pharmacologyMaleMotor Activity/drug effectsRatsRats, Sprague-DawleySwimming/psychology
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.
0091-3057 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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