Analysis of a Novel Cocaine Induced Immediate Early Gene

新型可卡因诱导立即早期基因的分析

• 批准号: 8233422
• 负责人: PAUL F WORLEY
• 金额: $ 64.67万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-20 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233422
• 关键词: Behavioral; Cocaine; Complex; Dopamine Receptor; Drug Addiction; Genes; Genetic; Goals; Growth Factor; Homer protein; Immediate-Early Genes; Mus; Neurons; Output; Pathway interactions; Pharmacology; Primates; Property; Protein Binding; Proteins; Rodent; Role; Signal Pathway; Signal Transduction; Stream; Synaptic plasticity; System; addiction; metabotropic glutamate receptor type 1; neurobehavioral; novel; prevent; receptor; response

We are examining how group 1 metabotropic glutamate receptors modify neuronal function and synaptic plasticity. This scientific goal is relevant to drug addiction since genetic deletion of mGluRS prevents neurobehavioral actions of cocaine Including behavioral activation and cocaine sensitization (Chiamulera et al., 2001). Moreover, mGluRS antagonists block behavioral responses to cocaine in rodents (Herzig and Schmidt, 2004) and primates (Lee et al., 2005; Paquet and Smith, 2003). One of our central hypotheses is that actions of mGIuR that are criticai for addition are transduced through the acton of a regulated adaptor system, that includes constitutively expressed Homer proteins together with an Immediate eariy gene fomn of Homer (H1 a). Homer proteins bind the C-terminus of group 1 metabotropic glutamate receptors as well as proteins that are down stream of mGluR in its various signaling pathways, and by self multimerization Homer can assemble these proteins into signaling complexes. The actions of Homer on mGluR signaling are complex and remari^ably elegant; Homer can regulate pharmacology of the receptor (Ango et al., 2001), the amplitude of the output and ability of the mGluR to receive convergent signals from dopamine receptors (DR) and growth factors including TritB. These pathways appear important for an understanding of the role of mGluR in addiction since genetic deletion of Homer results in enhanced sensitivity of mice to the addictive properties of cocaine

我们正在研究1组1代谢型谷氨酸受体如何修饰神经元功能和突触 可塑性。这种科学目标与吸毒有关，因为遗传缺失mglurs阻止了 可卡因的神经行为作用，包括行为激活和可卡因敏化（Chiamulera等， 2001）。此外，mglurs拮抗剂阻止了啮齿动物中对可卡因的行为反应（Herzig和Schmidt， 2004年）和灵长类动物（Lee等，2005； Paquet和Smith，2003）。我们的核心假设之一是行动 Mgiur被批评的批评是通过受管制适配器系统的acton进行了转导的， 包括组成型表达的荷马蛋白，以及荷马的立即耳朵基因（H1 A）。 荷马蛋白结合1组1组代谢型谷氨酸受体的C末端以及蛋白 MGlur在其各种信号通路中的下降流，并且通过自我多聚化可以组装 这些蛋白质成信号复合物。荷马对MGLUR信号传导的作用很复杂，并且 remari^非常优雅；荷马可以调节受体的药理学（Ango等，2001）， MGLUR从多巴胺受体（DR）接收收敛信号的能力和能力 包括Tritb在内的因素。这些途径对于理解MGlur在 成瘾由于荷马的遗传缺失导致小鼠对成瘾性的敏感性增强 可卡因