CORTICO-LIMBIC INTERACTIONS IN DRUG ABUSE

药物滥用中的皮质边缘相互作用

• 批准号: 2116125
• 负责人: JEANNIE L GIACCHINO
• 金额: $ 8.06万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-20 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2116125
• 关键词: 6 hydroxydopamine; acetylcholine; amygdala; brain electrical activity; brain mapping; dopamine; drug addiction; drug addiction antagonist; experimental brain lesion; frontal lobe /cortex; gamma aminobutyrate; glutamates; heroin; iontophoresis therapy; laboratory rat; lidocaine; neuropharmacology; neurotransmitters; nucleus accumbens; opioid receptor; self medication

The overall objectives of the research proposed for the five year period of the award are directed towards clarification of the neural substrates underlying opiate drug-related reinforcement and investigation of the role of endogenous neurotransmitters in these circuits. These studies will focus on structures within the rat limbic system, as well as their interaction with the nucleus accumbens, in an attempt to establish a more cohesive model for the processing and integration of stimuli related to drug motivated behaviors. Extracellular recording of field responses (evoked by either anti- or orthodromic stimulation of the nucleus accumbens) and spontaneous or driven unit firing from the medial prefrontal cortex, basolateral amygdala and the nucleus accumbens will be investigated in both anesthetized and freely-moving rats. The specific objectives of these studies will be (i) to electrophysiologically characterize medial prefrontal cortical neurons and to determine the effect of both systemically (I.V. or I.P.) or locally applied (iontophoresis) opiates on these cells, (2) to evaluate the neurophysiology and opiate neuropharmacology of the basolateral amygdaloid nucleus in a similar manner, (3) to determine the relative importance of input from these two limbic structures on the electrophysiologic activity of the nucleus accumbens "core" and "shell" sites (via electrical or pharmacological stimulation of these areas), (4) to evaluate the potential role of endogenous dopamine, GABA, glutamate and acetylcholine in the acute effects of opiates on the medial prefrontal cortex and basolateral nucleus of the amygdala. This series of experiments will involve the iontophoretic application of these agents (and their specific receptor agonists and antagonists) during systemic application of heroin, and (5) to define the function and potential interrelation of neurons in the media prefrontal cortex and the basolateral amygdala in unanesthetized, freely- moving rats involved in a heroin self-administration protocol. The outlined studies will establish an integrated research and training program delineating new aspects of drug abuse-related brain mechanisms, and potentially assisting in the development of treatment strategies. In addition, this project should provide an excellent opportunity for the clinician-researcher to gain scientific expertise in the complex and pertinent area of substance abuse.

五年期间提出的研究的总体目标 该奖项的旨在澄清神经基板 基本的鸦片药物相关的增强和对角色的研究 这些电路中的内源性神经递质。 这些研究会 专注于大鼠边缘系统内的结构及其 与伏隔核的相互作用，以建立更多 与刺激的处理和整合相关的凝聚模型 毒品动机行为。 细胞外记录现场反应 （通过抗细胞核的抗或正差刺激引起 a伏省），从内侧发射自发或驱动的单元 前额叶皮层，基底外侧杏仁核和伏隔核将是 在麻醉和自由移动的大鼠中进行了调查。具体 这些研究的目标将是（i）到电生理学 表征内侧前额叶皮质神经元并确定 系统地（i.v.或i.p.）或本地应用的效果 （离子噬菌体）对这些细胞进行鸦片，（2）评估 神经生理学和基底外侧杏仁核神经药理学 核以类似的方式，（3）确定 来自这两个边缘结构的电生理活性的输入 伏隔核的“核心”和“壳”位点（通过电气或 对这些区域的药理刺激），（4）评估潜力 内源性多巴胺，GABA，谷氨酸和乙酰胆碱在 阿片类药物对内侧前额叶皮层和基底外侧的急性作用 杏仁核的核。 这一系列实验将涉及 这些药物的离子噬菌体应用（及其特定受体 激动剂和拮抗剂）在全身应用海洛因时，（5） 定义培养基中神经元的功能和潜在相互关系 前额叶皮层和基底外侧杏仁核，一式自由度，自由地 - 涉及海洛因自我管理方案的大鼠移动大鼠。 这 概述的研究将建立综合研究和培训 计划描述与药物滥用相关的大脑机制的新方面， 并有可能协助制定治疗策略。 在 此外，该项目应该为 临床医生研究人员获得了综合体的科学专业知识 相关的药物滥用领域。