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Simvastatin Blocks Reinstatement of Cocaine-induced Conditioned Place Preference in Male Mice with Brain Lipidome Remodeling
Neuroscience Bulletin ( IF 5.9 ) Pub Date : 2021-09-07 , DOI: 10.1007/s12264-021-00771-z
Wei Xu 1, 2, 3 , Yuman He 1 , Jiamei Zhang 1 , Hongchun Li 1 , Xuemei Wan 1 , Menglu Li 1 , Yonghai Wang 4 , Rui Xu 1 , Haoluo Zhang 1 , Yanping Dai 1 , Haxiaoyu Liu 4 , Linhong Jiang 1 , Ying Zhao 1 , Xiaobo Cen 1
Affiliation  

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.



中文翻译:

辛伐他汀阻断可卡因诱导的大脑脂质组重塑雄性小鼠条件性位置偏爱的恢复

与药物相关的奖励记忆有助于强烈的渴望并经常引发复发。辛伐他汀已被证明可以调节参与记忆形成的脂质,但它对其他认知过程的影响尚不清楚。在这里,我们使用基于质谱的脂质组学方法来评估辛伐他汀在可卡因诱导的恢复范例中对小鼠大脑的影响。我们发现辛伐他汀阻止了可卡因诱导的条件性位置偏好 (CPP) 的恢复,而不影响 CPP 的获取。具体来说,只有在灭绝期间服用辛伐他汀才能阻止可卡因引发的恢复。全局脂质组分析表明,伏隔核是辛伐他汀引起的变化程度最大的区域。脂肪酸、磷脂和三酰甘油的代谢受到深刻影响。辛伐他汀逆转了可卡因诱导的对磷脂的大部分影响。相关矩阵显示可卡因和辛伐他汀显着重塑了特定大脑区域的脂质代谢途径。此外,辛伐他汀几乎逆转了由可卡因引起的脂肪酰基结构和不饱和度的所有变化。总之,使用辛伐他汀进行消退前治疗可促进可卡因消退并防止可卡因因脑脂质组重塑而复发。

更新日期:2021-09-08
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