Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats.
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.
Renshaw
Perry F
PF
Department of Psychiatry, Harvard Medical School, Belmont, MA 02478, USA. perry.renshaw@hsc.utah.edu
Parsegian
Aram
A
Yang
C Kevin
CK
Novero
Aileen
A
Yoon
Sujung J
SJ
Lyoo
In Kyoon
IK
Cohen
Bruce M
BM
Carlezon
William A
WA
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
D000928:Antidepressive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D005473:Fluoxetine; D008148:Lovastatin