Neurochemistry of Cocaine Reinforcement

描述（由申请人提供）：据报告， 刺激、强化和成瘾特性等。共识 中皮质边缘多巴胺与可卡因有关 大鼠自我给药，有研究表明， 皮质酮可能参与可卡因强化。几项研究 表明可卡因的交付环境可以改变行为和 对药物的神经化学反应，强调使用 在评估神经机制时， 加固.在本申请中要检验的假设是， 与可卡因自我管理相关的药物寻求行为引发了一种 一系列涉及多巴胺能系统相互作用的事件， 大脑与下丘脑-垂体-肾上腺（HPA）轴，这取决于 药物介绍的背景，即，药物是否主动给药 或者被动地注入。为了检验这一假设，有必要 成功地联合收割机复杂的行为实验（自我管理和 轭输注）与复杂的神经化学程序，在体内 微透析从不同的大脑区域被认为是参与了 寻求可卡因行为的调解。首先，体内微透析耦合 高效液相色谱法（HPLC）将用于测定 微透析液中多巴胺和皮质酮的浓度 从大鼠的内侧前额叶皮层收集，以响应几个 可卡因剂量在第二个实验中，将进行有限剂量反应。 使用具有多巴胺的HPLC分析的体内微透析进行， 在微透析样品中的皮质酮的放射免疫测定， 杏仁核的中央核这项研究的结果将决定 中脑边缘和中皮层多巴胺能投射在药物中作用 成瘾，证明是否神经化学反应， 自我管理的可卡因是不同的，观察后，被动 注射可卡因采用微透析与 三重结合模型将使我们能够区分可卡因的激活作用， HPA轴的激活与药物寻求有关 行为（即，自我给药与被动输注可卡因）。因此 这些实验的结果将证明如何控制药物输送 可以影响荷尔蒙输入对功能特征的影响， 神经系统的特定解剖投影。这些结果将 也提供了类固醇激素在塑造中所起作用的证据。 大脑的功能活动。

DESCRIPTION (provided by applicant): Cocaine has been reported to have stimulant, reinforcing and addictive properties, among others. A consensus exists that mesocorticolimbic dopamine is involved in cocaine self-administration in rats and there are studies suggesting that corticosterone may be involved in cocaine reinforcement. Several studies have demonstrated that the context of cocaine delivery can alter the behavioral and neurochemical responses to the drug, emphasizing the importance of using appropriate behavioral models when assessing neural mechanisms of reinforcement. The hypothesis to be tested in this application is that drug-seeking behavior associated with cocaine self-administration triggers a sequence of events involving the interaction of dopaminergic systems in the brain with the hypothalamo-pituitary-adrenal (HPA) axis, which depends on the context of drug presentation, i.e., whether the drug is actively administered or infused passively. To test this hypothesis, it will be necessary to successfully combine the complex behavioral experiment (self-administration and yoked infusions) with the complex neurochemical procedure, in vivo microdialysis from different brain areas thought to be involved in the mediation of cocaine-seeking behavior. First, in vivo microdialysis coupled with high performance liquid chromatography (HPLC) will be used to determine the concentrations of dopamine and corticosterone in the microdialysates collected from the medial prefrontal cortex of rats in response to several doses of cocaine. In the second experiment, a limited dose response will be performed using in vivo microdialysis with the HPLC analysis of dopamine and radioimmunoassay of corticosterone in the microdialysis samples collected from the central nucleus of the amygdala. The results of this study will determine the role of mesolimbic and mesocortical dopaminergic projections in drug addiction, demonstrating whether or not the neurochemical response to self-administered cocaine is different from that observed after the passive infusions of cocaine. Using the combination of microdialysis with the yoked-triad model will allow us to distinguish the activating effect of cocaine on the HPA axis from the activation of the HPA axis related to drug-seeking behavior (i.e., self-administration vs. passively infused cocaine). Thus, the results of these experiments will demonstrate how control over drug delivery can affect the influence of a hormonal input on the functional characteristics of specific anatomical projections of the neural system. These results will also provide evidence of the role that is played by steroid hormones in shaping the functional activity of the brain.