Dowd Sarah E, Mustroph Martina L, Romanova Elena V, Southey Bruce R, Pinardo Heinrich, Rhodes Justin S, Sweedler Jonathan V
Department of Chemistry, Neuroscience Program, Beckman Institute, Department of Animal Sciences, and Department of Psychology, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, 63-5, Urbana, Illinois 61801, United States.
ACS Omega. 2018 Oct 31;3(10):13817-13827. doi: 10.1021/acsomega.8b01713. Epub 2018 Oct 24.
Recent research suggests that exercise may help facilitate abstinence from cocaine addiction, though the mechanisms are not well understood. In mice, wheel running accelerates the extinction of conditioned place preference (CPP) for cocaine, providing an animal model for evaluating potential neurological mechanisms. The objective of this study was to quantify dynamic changes in endogenous peptides in the amygdala and dentate gyrus of the hippocampus in mice exposed to a context paired with the effects of cocaine, and in response to exercise. Male C57BL/6J mice conditioned to cocaine were housed with or without running wheels for 30 days. Following a CPP test and final exposure to either a cocaine- or saline-associated context, peptides were measured in brain tissue extracts using label-free matrix-assisted laser desorption/ionization mass spectrometry (MS) and stable isotopic labeling with liquid chromatography and electrospray ionization MS. CPP in mice was significantly reduced with running, which correlated to decreased myelin basic protein derivatives in the dentate gyrus extracts, possibly reflecting increased unmyelinated granule neuron density. Exposure to a cocaine-paired context increased hemoglobin-derived peptides in runners and decreased an actin-derived peptide in sedentary animals. These results allowed us to characterize a novel set of biomarkers that are responsive to exercise in the hippocampus and in a cocaine-paired context in the amygdala.
最近的研究表明，运动可能有助于促进戒除可卡因成瘾，尽管其机制尚不清楚。在小鼠中，轮转运动加速了对可卡因的条件性位置偏爱（CPP）的消退，为评估潜在的神经机制提供了一种动物模型。本研究的目的是量化暴露于与可卡因效应相关的环境中的小鼠，以及在运动反应中，海马杏仁核和齿状回内源性肽的动态变化。将条件性适应可卡因的雄性C57BL/6J小鼠饲养在有或没有转轮的环境中30天。在进行CPP测试并最终暴露于与可卡因或生理盐水相关的环境后，使用无标记基质辅助激光解吸/电离质谱（MS）以及液相色谱和电喷雾电离MS的稳定同位素标记法，测量脑组织提取物中的肽。运动使小鼠的CPP显著降低，这与齿状回提取物中髓鞘碱性蛋白衍生物的减少相关，可能反映了无髓鞘颗粒神经元密度的增加。暴露于与可卡因配对的环境中，使跑步小鼠体内血红蛋白衍生肽增加，而使久坐不动的动物体内肌动蛋白衍生肽减少。这些结果使我们能够鉴定出一组新的生物标志物，它们在海马体以及杏仁核中对可卡因配对环境的反应中对运动有反应。
