NUCLEUS ACCUMBENS, COCAINE REWARD & RECOVERY

该项目的长期目标是评估和确定 可卡因的代谢和药理作用机制 与大鼠伏隔核(NAC)相关的神经元回路，一个关键的 多巴胺能奖赏区域，在慢性治疗和早期戒断期间。 多巴胺激动剂在代谢恢复中的治疗潜力 将对禁欲进行评估，以便更好地了解有益的 可卡因滥用的治疗方法。该项目的具体目标是：(1) 描述慢性可卡因治疗对功能活动的影响 在NAC中使用葡萄糖利用和药物受体的标记物 本地区受可卡因影响，(2)确定可卡因的作用机制 慢性可卡因诱导的NAC的差异激活，(3)评估 脑功能活动选择性减退的幅度和时间进程 可卡因戒断期间的NAC，以及(4)研究假定的增强 在此期间由多巴胺激动剂诱导的代谢恢复。这个 定量[14C]2-脱氧葡萄糖(2DG)放射自显影方法 用来检测慢性可卡因治疗对血糖的影响 在与NAC相关的脑回路中的应用，并遵循选择性 大脑区域的神经元和神经化学损伤，如内侧 前额叶皮质，它被证明投射到受影响的 南汽的一部分。因此，这些代谢效应的潜在机制 可卡因的种类将会得到澄清。这些区域代谢数据的相关性 随着慢性可卡因治疗区域研究的结果 体外受体放射自显影测定多巴胺和阿片受体水平 来自同一脑组织的相邻切片将进一步阐明 潜在的机制。多巴胺激动剂的药物治疗效果 在可卡因戒断期间，NAC代谢的研究也将使用 2DG方法。总之，这些研究将确定慢性可卡因如何 治疗引起NAC代谢改变，并将测试 慢性可卡因使用后的药物治疗效果。

The long-term objectives of the project are to assess and determine the mechanism underlying the metabolic and pharmacologic effects of cocaine in neuronal circuits related to the rat nucleus accumbens (NAc), a critical dopaminergic reward region, during chronic treatment and early abstinence. The therapeutic potential of dopamine agonists on metabolic recovery during abstinence will be evaluated, allowing a better understanding of beneficial therapies for cocaine abuse. The specific aims of the project are (1) to characterize the effect of chronic cocaine treatment on functional activity in NAc using markers for glucose utilization and pharmacologic receptors affected by cocaine in this region, (2) to determine the mechanism of chronic cocaine-induced differential activation of NAc, (3) to assess the magnitude and time course of selective reduction of functional activity in NAc during cocaine abstinence, and (4) to study the putative enhancement of metabolic recovery induced by dopamine agonists during this period. The quantitative [14C]2-deoxyglucose (2DG) autoradiographic method will be employed to examine the effect of chronic cocaine treatment on glucose utilization in brain circuits related to the NAc, and following selective neuronal and neurochemical lesions in brain regions, such as medial prefrontal cortex, which are demonstrated to project to the affected portions of NAc. Thus, the underlying mechanism of these metabolic effects of cocaine will be elucidated. Correlation of these regional metabolic data with the results of studies of chronic cocaine treatment on regional dopamine and opiate receptor levels using in vitro receptor autoradiography in adjacent sections from the same brain tissue will further elucidate the underlying mechanism. The effect of pharmacotherapy with dopamine agonists during cocaine abstinence on NAc metabolism will also be investigated using the 2DG method. Together, these studies will determine how chronic cocaine treatment causes NAc metabolic alteration, and will test pharmacotherapeutic efficacy following chronic cocaine use.