Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI.
Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI.
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DOI：
10.1002/nbm.3409
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发表时间：
2015-11
影响因子：
2.9
通讯作者：
Berkowitz BA
中科院分区：
文献类型：
--
作者：
Perrine SA;Ghoddoussi F;Desai K;Kohler RJ;Eapen AT;Lisieski MJ;Angoa-Perez M;Kuhn DM;Bosse KE;Conti AC;Bissig D;Berkowitz BA
药物滥用研究的一个长期目标是将药物诱导的行为结果与特定大脑区域的活动联系起来，以了解成瘾行为的神经生物学并寻找药物靶点。在这里，我们测试了可卡因产生运动（行为）敏化的假设，这与增加钙通道介导的神经活性与药物成瘾相关的大脑区域，如脑桥核（NAC），前纹状体（AST）和海马，如使用锰增强磁共振成像（MEMRI）测量。大鼠用可卡因处理5天，然后是2天的停药期。第二天，在锰的存在下，将运动敏化定量为可卡因诱导的神经可塑性的度量。在行为测试后，立即使用MEMRI检查大鼠NAC、AST、海马和颞肌中与行为敏化相关的钙通道介导的神经元活性的变化。与盐水处理对照组大鼠相比，皮质醇显著增加了自发活动并产生了行为敏化。与盐水处理的对照大鼠相比，在可卡因处理的大鼠的NAC中确定了MEMRI信号强度的显著增加，而不是AST或海马。皮质醇没有增加颞肌的信号强度。值得注意的是，为了支持我们的假设，行为与NAC中的MEMRI信号强度显著正相关。由于神经元对锰的摄取受钙通道的调节，这些结果表明MEMRI是一种强大的研究工具，可以研究自由行为动物的神经元活动，并指导新的基于钙通道的治疗可卡因滥用和依赖的疗法。
A long-standing goal of substance abuse research has been to link drug-induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and search for drug-able targets. Here we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel-mediated neuroactivity in brain regions linked with drug addiction such as, the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese-enhanced magnetic resonance imaging (MEMRI). Rats were treated with cocaine for 5-days followed by a 2-day drug-free period. The following day, locomotor sensitization was quantified as a metric of cocaine-induced neuroplasticity, in the presence of manganese. Immediately following behavioral testing, rats were examined for changes in calcium channel-mediated neuronal activity in the NAC, AST, hippocampus, and temporalis muscle that was associated with behavioral sensitization using MEMRI. Cocaine significantly increased locomotor activity and produced behavioral sensitization compared to saline-treatment to control rats. A significant increase in MEMRI signal intensity was determined in the NAC, but not AST or hippocampus, of cocaine-treated rats compared to saline-treated control rats. Cocaine did not increase signal intensity in the temporalis muscle. Notably, in support of our hypothesis, behavior was significantly and positively correlated with MEMRI signal intensity in the NAC. Since neuronal uptake of manganese is regulated by calcium channels, these results indicate that MEMRI is a powerful research tool to study neuronal activity in freely behaving animals and to guide new calcium channel-based therapies for treating cocaine abuse and dependence.