REGULATION OF MESOLIMBIC DOPAMINE BY ENDOGENOUS COMPOUND

内源性化合物对中脑边缘多巴胺的调节

• 批准号: 2245056
• 负责人: Peter W Kalivas
• 金额: $ 10.38万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2245056
• 关键词: behavioral habituation /sensitization; brain mapping; dopamine; dopamine receptor; experimental brain lesion; gamma aminobutyrate; glutamates; high performance liquid chromatography; in situ hybridization; laboratory rat; limbic system; microdialysis; microinjections; motor cortex; neural information processing; neural transmission; neuroanatomy; neurochemistry; neurotransmitter metabolism; neurotransmitter receptor; nucleus accumbens; psychomotor function; receptor expression; stereotaxic techniques

A dysfunction of the brain circuitry mediating the translation of relevant environmental stimuli into adaptive motor responses is thought to have an etiologic or permissive role in many psychiatric disorders. Classic limbic structures provide emotional and cognitive context to environmental stimuli. The circuitry whereby this information is transferred to motor systems and the appropriate behavioral response initiated involves a series of nuclei possessing extensive reciprocal interconnectivity. This circuit is referred to as the 'motive circuit' and includes the ventral tegmental area, nucleus accumbens, ventral pallidum, mediodorsal thalamus, prefrontal cortex and pedunculopontine motor area. The goal of this continuation proposal is to functionally map the flow of information from limbic to motor nuclei through the motive circuit. This will be accomplished using three convergent technologies, 1) retrograde labeling of neurons combined with in situ hybridization for mRNA of relevant transmitter-related proteins, 2) intracranial infusions of transmitter analogues into the circuit to map the connections mediating behavioral activation, and 3) microinjecting transmitter analogues into the circuit and measuring changes in extracellular transmitter concentrations with microdialysis. The proposal is based upon three general hypotheses. 1) A detailed topography exists which permits the transfer of information into discrete compartments within nuclei comprising the motive circuit. 2) The selective transfer of information is, to some extent, chemically coded such that different neurotransmitters route information through different efferent projections. 3) The routing of information is under environmental/genetic control. This latter hypothesis relies on recent observations that the intensity of the motor response elicited by rats in a novel environment is correlated with neurochemical alterations in subnuclei of the motive circuit. Thus, prior to beginning all experiments, rats will be behaviorally screened in a novel open field to permit correlations between their motor response to novelty and other subsequent measures. Many behavioral symptoms defining psychiatric illnesses involve inappropriate behavioral responses to environmental stimuli. The motive circuit is responsible for translating environmental stimuli into adaptive motor responses. By understanding the anatomical and chemical organization of the motive circuit it will be possible to pharmacologically modulate inappropriate behaviors with greater accuracy. Furthermore, the anatomical and functional mapping of the motive circuit will provide a basis for interpreting future imaging studies in humans where attempts are made to correlate changes in spatially discrete nuclei.

大脑回路介导相关信息翻译的功能障碍 环境刺激转化为适应性运动反应被认为具有 在许多精神疾病中的病因或许可作用。 典型的边缘系统 结构为环境提供情感和认知背景 刺激。 将这些信息传送到电机的电路 系统和适当的行为反应启动涉及一系列 具有广泛相互连接性的原子核。 该电路 被称为“运动回路”，包括腹侧被盖 腹侧苍白球，丘脑背内侧区，前额叶 皮质和脚桥脑运动区。 这种延续的目的是 建议是功能性地映射信息流从边缘系统到 运动神经核通过运动回路。 这将通过使用 三种聚合技术，1）结合神经元的逆行标记 原位杂交检测相关递质相关的mRNA 蛋白质，2）将递质类似物颅内输注到 映射介导行为激活的连接的电路，以及3） 向回路中微量注射递质类似物， 细胞外递质浓度。 该建议基于三个一般假设。 1)详细 地形的存在，它允许信息转移到离散的 核内的隔室包括运动电路。 2)选择性 信息的传递在某种程度上是化学编码的， 不同的神经递质通过不同的传出神经传递信息 预测。 3)信息的传递是根据环境/遗传 控制 后一种假设依赖于最近的观察， 在新环境中由大鼠引起的运动反应的强度是 与运动亚核的神经化学改变相关 电路. 因此，在开始所有实验之前，大鼠将 在新的开放领域进行行为筛选，以允许之间的相关性 他们对新奇事物的运动反应和其他后续措施。 许多定义精神疾病的行为症状包括 对环境刺激的不当行为反应 动机 一个电路负责将环境刺激转化为适应性刺激， 运动反应 通过了解其解剖学和化学结构 将有可能对原动机电路的 不恰当的行为更准确。 此外，解剖学 以及运动电路的功能映射将为 解释未来的人类成像研究，其中试图 关联空间离散核的变化。