Abstract
Statins are drugs that have been used for decades in humans for the treatment of hypercholesterolemia. More recently, several lines of evidence demonstrate that statins, in addition to their peripheral effects, produce a wide variety of effects in the brain and may be beneficial in neurological and psychiatric conditions. In this study, we allowed rats to self-administer cocaine for several weeks and, at the end of self-administration training, we treated them with low doses of statins daily for a 21-day period of abstinence. Chronic administration of brain-penetrating statins, simvastatin (1 mg/kg) and atorvastatin (1 mg/kg), reduced cocaine seeking compared with vehicle, whereas administration of pravastatin (2 mg/kg), a statin with low brain penetrability, did not. Importantly, the effects of brain-penetrating statins persisted even after discontinuation of the treatment and were specific for drug seeking because drug taking was not altered by simvastatin treatment. Finally, the effects of simvastatin were found to generalize to another drug of abuse such as nicotine, but not to food reward, and to reinstatement of cocaine seeking induced by stress. These results demonstrate that brain-penetrating statins can reduce risks of relapse to addiction. Given their well-known safety profile in humans, statins could be a novel effective treatment for relapse to cocaine and nicotine addiction and their use could be implemented in clinical settings without major health risks.
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Acknowledgements
We thank PO Fernagut and M Mameli for helpful comments on a previous version of the manuscript. We thank Ranbaxy Laboratories Limited for generously providing simvastatin. This work was supported by the Institute National de la Santé et de la Recherche Medical, le Centre National pour la Recherche Scientifique, University of Poitiers, and the Contrat de Projet Etat Region (CPER) and the Fonds Européens de Développement Régional (FEDER) programs. This study was supported by a CNRS PEPS grant to MS. CC was recipient of a PhD fellowship from the French Minister of research; CN was recipient of a PhD fellowship from the Poitou-Charentes region.
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Chauvet, C., Nicolas, C., Lafay-Chebassier, C. et al. Statins Reduce the Risks of Relapse to Addiction in Rats. Neuropsychopharmacol 41, 1588–1597 (2016). https://doi.org/10.1038/npp.2015.317
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DOI: https://doi.org/10.1038/npp.2015.317
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