title: Statins Reduce the Risks of Relapse to Addiction in Rats.
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.
authors.affiliation: Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.|University of Poitiers, 1 Rue George Bonnet, Poitiers, France.
authors.forename: Claudia
authors.initials: C
authors.lastname: Chauvet
authors.affiliation: Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.|University of Poitiers, 1 Rue George Bonnet, Poitiers, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Nicolas
authors.affiliation: Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.|University of Poitiers, 1 Rue George Bonnet, Poitiers, France.|Department of Clinical Pharmacology, Poitiers University Hospital, Poitiers, France.|Inserm, CIC 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lafay-Chebassier
authors.affiliation: Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.|University of Poitiers, 1 Rue George Bonnet, Poitiers, France.|Inserm, CIC 1402, Poitiers University Hospital, Poitiers, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jaber
authors.affiliation: Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.|University of Poitiers, 1 Rue George Bonnet, Poitiers, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thiriet
authors.affiliation: Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.|University of Poitiers, 1 Rue George Bonnet, Poitiers, France.
authors.forename: Marcello
authors.identifier: http://orcid.org/0000-0002-0664-5964
authors.initials: M
authors.lastname: Solinas
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012307:Risk Factors; D019821:Simvastatin / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D019821:Simvastatin