Role of Striatopallidal Neurons in Drug-Induced Neural Plasticity and Behavior

纹状体苍白球神经元在药物诱导的神经可塑性和行为中的作用

• 批准号: 8279177
• 负责人: Susan Marie Ferguson
• 金额: $ 23.67万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279177
• 关键词: Amphetamines; Animal Model; Behavior; Behavioral; Brain region; Cells; Cocaine; Corpus striatum structure; Designer Drugs; Development; Drug Addiction; Drug Exposure; Dynorphins; Economic Burden; Efferent Pathways; Enkephalins; Epidemic; FOS gene; Future; Gene Expression; Gene Transfer; Human; Immediate-Early Genes; Lead; Maintenance; Mediating; Molecular; Molecular Genetics; Mus; Neuronal Plasticity; Neurons; Neuropeptides; Nucleus Accumbens; Pathway interactions; Pharmaceutical Preparations; Population; Process; Public Health; Rattus; Research; Role; Self Administration; Societies; Substance P; Techniques; Therapeutic Intervention; Transgenic Mice; Viral; Viral Vector; Work; addiction; brain behavior; drug seeking behavior; neural circuit; novel; prevent; psychostimulant; receptor; research study; social; tool

Tlie striatum is mostly comprised of GABAergic medium spiny projection neurons (MSNs) tlnat differ in thieir neuropeptide expression and form two major efferent patiiways. MSNs that contain the neuropeptides dynorptiin and substance P are part of the striatonigral, or 'direct', pathway whereas MSNs that contain the neuropeptide enl<ephalin are part of the striatopallidai, or 'indirect', pathway. Psychostimulant-induced alterations in the striatum are thought to be critical in the development and maintenance of drug addiction; however, the role of specific striatal cell populations is not clear. Nonetheless, recent evidence suggests that striatopallidai neurons may be especially important for the long-term changes in brain and behavior produced by drugs. For example, studies using immediate early gene expression as an indicator of neuronal activity found that while mere psychostimulant exposure is sufficient to increase activity in striatonigral neurons, only drug exposure under conditions that lead to forms of drug-induced behavioral plasticity, such as psychomotor sensitization, also activates striatopallidai neurons. The overall aim of the proposed experiments is to use novel molecular and genetic targeting approaches to directly examine the involvement of striatopallidai MSNs in drug-induced molecular changes and behavioral plasticity. It is hypothesized that recruitment of striatopallidai neurons is critical for the long-term changes in striatal gene expression induced by psychostimulants, as well as in the development and expression of psychomotor sensitization and the escalation of drug self-administration behavior. This work will help to elucidate the contribution of striatopallidai medium spiny neurons in the processes that underlie addiction; In addition, precise identification ofthe neural circuits that regulate the transition to addiction should be useful for guiding the development of future treatments for addicts.

纹状体主要由GABA能中型多棘投射神经元（MSN）组成，它们在功能上不同。 神经肽的表达和形成两个主要的传出途径。含有神经肽 强啡肽和P物质是纹状体黑质或“直接”途径的一部分，而含有强啡肽和P物质的MSN是纹状体黑质或“直接”途径的一部分。 神经肽enl<ephalin是纹状体通路或“间接”通路的一部分。精神兴奋剂诱导的 纹状体的改变被认为在药物成瘾的发展和维持中至关重要; 然而，特定的纹状体细胞群的作用尚不清楚。尽管如此，最近的证据表明， 纹状体皮质神经元可能对大脑和行为产生的长期变化特别重要 被毒品例如，使用即时早期基因表达作为神经元活动指标的研究 发现，虽然仅仅是精神兴奋剂暴露足以增加纹状体黑质神经元的活动，但只有 在导致药物诱导的行为可塑性形式的条件下暴露于药物，例如 精神致敏也激活纹状体神经元。建议的总体目标 实验是使用新的分子和遗传靶向方法直接检查参与 药物诱导的分子变化和行为可塑性中的作用。它是假设 纹状体苍白球神经元的募集对于诱导纹状体基因表达的长期变化至关重要。 精神刺激剂，以及在发展和表达的精神敏化和 自我给药行为升级。这项工作将有助于阐明的贡献 纹状体中棘神经元在成瘾的基础过程中;此外，精确 识别调节成瘾过渡的神经回路应该有助于指导 未来的治疗药物的发展。