NEUROPHYSIOLOGICAL ASSESSMENT OF COCAINE REINFORCEMENT

药物滥用神经生物学研究中心项目0003 将研究伏隔核(NA)和其他脑的作用 非人类可卡因自我给药的控制区域 灵长类动物。这些研究的目的是明确地确定 不同词组在药物输注中的内部编码 猴子在NA细胞中刺激的放电模式类似于 在先前资助的大鼠自我给药模型中展示 中心的时期。将这些研究扩展到非人类 灵长类动物提供了一种更有信息量的评估和 几种不同大脑中单个和多个神经元活动的特征 同时在更复杂的刺激情况下的地区 以及在啮齿类动物中所能实现的上下文控制。实验是 旨在确定NA之外的哪些大脑区域是至关重要的 激活或抑制单个神经元的放电变化，在 可卡因自我给药和在评估有效可卡因期间 相似范例中的类似物(黄连)。候选脑区 被调查的是那些受急性可卡因注射影响最大的人 或自身注射可卡因，如2-DG代谢成像所示 猴子的地图。这些细胞包括，NA(外壳和核心)，多巴胺能细胞 腹侧被盖区(VTA)、杏仁核(内侧和基底)、 海马体(CA1和下丘)：扣带回和眼眶前叶皮质。 在大多数情况下，这些区域向NA提供传入投射。 因此将与NA同时进行检查以确定 有功能的下层底物的证据。进一步的研究将是 以确定NA和其他区域细胞激发的程度 模式由具有以下特征的刺激的关联属性控制 与毒品递送相匹配。特别是，研究将调查 无论是刺激，还是刺激发生的背景，都更多 与与药物和食欲配对形成的联系有关 奖励。另外，当这种联想形成时，这些刺激是 与更能改变户外行为的药物增强剂配对 与非毒品相关的增强剂相比，最初的奖励背景。 这种不同的加固能力应体现为不同 相关脑区的细胞放电模式，提供了进一步的 深入了解可卡因等药物如何影响激励过程和收获 对行为的控制。

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.