ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Animals , Male , Mice , Brain , Cocaine , Conditioning, Operant , Extinction, Psychological , Lipidomics , Simvastatin/therapeutic useABSTRACT
Objective To investigate the protective effects of warm oxygenated leukocyte-depleted blood cardioplegia on myocardium during cardiac valve replacement. Methods Forty patients of both sexes undergoing elective valve replacement under CPB were randomly allocated into two groups (n = 20 each) : control group and study group. Warm blood cardioplegia was used in both groups, while in study group the leukocytes in the blood used for cardioplegia were depleted with FT-RL type leukocyte filter. The T0 of the cardioplegic solution was maintained at 32-35℃. Blood samples were taken for determination of plasma concentrations of human heart fatty acid-binding protein (HH-FABP) and malonaldehyde (MDA) and myocardial tissue was obtained from right atrium for determination of myeloperoxidase (MPO) activity before aortic cross-clamping (T0), immediately after (T1) and 30 and 60 min after aortic unclamping (T2 ,T3).Results The two groups were comparable with regard to sex, age, body weight, height, cardiac function and CPB and aortic cross-clamping time. The plasma concentrations of HH-FABP and MDA were significantly increased after aortic unclamping (T2,3) compared to the baseline (T0) in both groups but were significantly lower in study group than in control group (P