Chauvet Claudia, Nicolas Celine, Lafay-Chebassier Claire, Jaber Mohamed, Thiriet Nathalie, Solinas Marcello
Inserm, U-1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France.
University of Poitiers, 1 Rue George Bonnet, Poitiers, France.
Neuropsychopharmacology. 2016 May;41(6):1588-97. doi: 10.1038/npp.2015.317. Epub 2015 Oct 15.
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.
他汀类药物已在人类中用于治疗高胆固醇血症数十年。最近，有几条证据表明，他汀类药物除了具有外周作用外，还会在大脑中产生多种作用，并且可能对神经和精神疾病有益。在本研究中，我们让大鼠自行服用可卡因数周，在自行给药训练结束时，我们在为期21天的戒断期内每天用低剂量的他汀类药物对它们进行治疗。与赋形剂相比，长期给予可穿透大脑的他汀类药物辛伐他汀（1毫克/千克）和阿托伐他汀（1毫克/千克）可减少对可卡因的觅求行为，而给予大脑穿透性低的他汀类药物普伐他汀（2毫克/千克）则没有这种作用。重要的是，即使在停止治疗后，可穿透大脑的他汀类药物的作用仍然持续存在，并且对觅药行为具有特异性，因为辛伐他汀治疗并未改变药物摄取。最后，发现辛伐他汀的作用可推广到另一种滥用药物，如尼古丁，但对食物奖励没有影响，并且对应激诱导的可卡因觅求行为的恢复也没有影响。这些结果表明，可穿透大脑的他汀类药物可以降低成瘾复发的风险。鉴于它们在人类中众所周知的安全性，他汀类药物可能是治疗可卡因和尼古丁成瘾复发的一种新型有效疗法，并且可以在临床环境中使用而不会有重大健康风险。
