Smith Hilary R, Beveridge Thomas J R, Nader Michael A, Porrino Linda J
Department of Physiology and Pharmacology, Center for the Neurobiology of Addiction Treatment (CNAT), Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
Department of Physiology and Pharmacology, Center for the Neurobiology of Addiction Treatment (CNAT), Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
Drug Alcohol Depend. 2014 Apr 1;137:143-7. doi: 10.1016/j.drugalcdep.2014.01.015. Epub 2014 Jan 30.
Neuroimaging studies of cocaine users have demonstrated white matter abnormalities associated with behavioral measures of impulsivity and decision-making deficits. The underlying bases for this dysregulation in white matter structure and function have yet to be determined. The aim of the present studies was to investigate the influence of prolonged cocaine self-administration on the levels of myelin-associated proteins and mRNAs in nonhuman primate white matter.
Rhesus monkeys (N=4) self-administered cocaine (0.3mg/kg/inj, 30 reinforcers per session) for 300 sessions. Control animals (N=4) responded for food. Following the final session monkeys were euthanized and white matter tissue at three brain levels was processed for immunoblotting analysis of proteolipid protein (PLP) and myelin basic protein (MBP), as well as for in situ hybridization histochemical analysis of PLP and MBP mRNAs.
Both MBP and PLP immunoreactivities in white matter at the level of the precommissural striatum were significantly lower in tissue from monkeys self-administering cocaine as compared to controls. No significant differences were seen for either protein at the levels of the prefrontal cortex or postcommissural striatum. In addition, no differences were observed in expression of mRNA for either protein.
These preliminary findings, in a nonhuman model of prolonged cocaine self-administration, provide further evidence that compromised myelin may underlie the deficits in white matter integrity described in studies of human cocaine users.
对可卡因使用者的神经影像学研究表明，白质异常与冲动行为和决策缺陷的行为指标相关。白质结构和功能失调的潜在原因尚未确定。本研究的目的是调查长期自我给药可卡因对非人类灵长类动物白质中髓磷脂相关蛋白和mRNA水平的影响。
恒河猴（N = 4）自我给药可卡因（0.3mg/kg/注射，每次30次强化），共300次。对照动物（N = 4）通过对食物做出反应来进行实验。在最后一次实验后，对猴子实施安乐死，并对三个脑水平的白质组织进行处理，用于蛋白脂蛋白（PLP）和髓磷脂碱性蛋白（MBP）的免疫印迹分析，以及PLP和MBP mRNA的原位杂交组织化学分析。
与对照组相比，自我给药可卡因的猴子组织中，连合前纹状体水平白质中的MBP和PLP免疫反应性显著降低。在前额叶皮质或连合后纹状体水平，两种蛋白质均未观察到显著差异。此外，两种蛋白质的mRNA表达也未观察到差异。
在长期自我给药可卡因的非人类模型中的这些初步发现，进一步证明了髓磷脂受损可能是人类可卡因使用者研究中所描述的白质完整性缺陷的基础。
