NEUROPHYSIOLOGICAL ASSESSMENT OF COCAINE REINFORCEMENT

药物滥用神经生物学研究中心0003项目 将研究脑桥核（NA）和其他脑功能的作用， 可卡因自我给药的管制区域 灵长类动物这些研究旨在明确确定 药物输注之间的内部不同短语的编码， 猴子在NA细胞中引起类似的放电模式， 在先前资助的大鼠自我给药模型中证明 中心时期。这些研究扩展到非人类 灵长类动物提供了一种信息量更大的评估手段， 表征几种不同大脑中的单个和多个神经元活动 同时在更复杂的刺激环境下， 和情境控制的能力。实验 旨在确定NA旁边的哪些大脑区域 在单个神经元放电变化方面被激活或抑制， 可卡因自我给药和强效可卡因评估期间 类似物（tropanes）在类似的范例。候选大脑区域 探索的是那些受急性可卡因注射影响最大的人， 或自身服用可卡因，如2-DG代谢成像所示 猴子的地图这些细胞包括NA（壳和核），多巴胺能细胞， 腹侧被盖区（VTA），杏仁核（内侧和基底）， 海马（CA 1和下托）扣带和眶额叶皮质。 在大多数情况下，这些区域向NA提供传入投射， 因此将与NA同时检查 功能性底层基质的证据。进一步的研究将 以确定NA和其他区域细胞放电的程度 模式是由刺激的联想属性控制的， 与药物输送相结合。特别是研究将调查 无论是刺激，还是刺激发生的环境， 与药物和食欲配对形成的关联有关 奖励此外，当这种联想形成时， 与更有能力改变外界行为的药物相结合， 与非药物相关的奖励者相比，原始奖励背景。 这种差异化的强化能力应体现为差异化的 在相关的大脑区域的细胞放电模式，提供进一步的 深入了解可卡因等药物如何影响动机过程和收益 控制行为。

Project 0003 in the Center for Neurobiological Investigation of Drug Abuse will investigate the role of nucleus accumbens (NA) and other brain regions in the control of cocaine self-administration in non-human primates. These studies are designed explicitly to determine whether encoding of different phrases of the internal between drug infusions in the monkey provokes similar patterns of discharge in NA cells as demonstrated in the rat-self administration model in the prior funding period of the Center. The extensions of those studies to the non-human primate provides for a more informative means of assessing and characterizing single and multi-neuron activity in several different brain regions simultaneously and under more complex circumstances of stimulus and context control than could be achieved in the rodent. Experiments are designed to determine what brain regions beside the NA are critically activated or inhibited in terms of single neuron firing changes, during cocaine self-administration and during assessment of potent cocaine analogs (tropanes) in similar paradigms. Candidate brain regions to be explored are those maximally affected by either acute cocaine injections or self-administration of cocaine as shown by imaging of 2-DG metabolic maps in monkeys. These include, NA (shell and core), dopaminergic cells in the ventral tegmental area (VTA), the amygdala (medial and basal), the hippocampus (CA1 and subiculum) the cingulate and orbital frontal cortex. These areas in most cases supply afferent projections to the NA in the monkey and therefore will be examined simultaneously with the NA for evidence of a functional underlying substrate. Further studies will be conducted to determine extent to which NA and other regional cell firing patterns are controlled by the associative properties of stimuli that have been paired with drug delivery. In particular studies will investigate whether the stimuli, or the contexts in which stimuli occur, are more relevant to the associations formed by pairing with drug versus appetitive reward. In addition when such associations are formed, are those stimuli paired with drug reinforcers more capable of modifying behavior outside the original reward context in comparison to non-drug related reinforcers. Such differential reinforcing capacity should be reflected as differential cell firing patterns in the implicated brain regions, providing further insight into how drugs like cocaine affect motivational processes and gain control over behavior.