Cocaine-induced plasticity in the nucleus accumbens

可卡因诱导的伏隔核可塑性

• 批准号: 6938282
• 负责人: AMY C BOUDREAU
• 金额: $ 3.21万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-04 至 2009-04-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938282
• 关键词: AMPA receptors; NMDA receptors; behavioral /social science research tag; behavioral habituation /sensitization; cocaine; dopamine receptor; drug addiction; laboratory rat; long term potentiation; neural plasticity; neuropharmacology; nucleus accumbens; predoctoral investigator; receptor expression

DESCRIPTION (provided by applicant): Although the past fifteen years of research has provided a wealth of insight into the neurobiological basis of drug addiction, society as a whole remains heavily impacted by drugs of abuse. More research is needed to further understand the cellular basis of the persistent behaviors associated with drug addiction (seeking, craving, and relapse to use) to help provide better treatment strategies to combat addiction. Our hypothesis is that addiction is a form of neuronal plasticity, perhaps an aberrant form of learning, similar in mechanism to other forms of plasticity, such as LTD and LTP. This research proposal will provide important information about the biochemical plasticity of the nucleus accumbens (NAc), a brain region important for the motivational aspects of behavior and essential in drug addiction. This will further our understanding of addictionrelated adaptations on the cellular level. Because LTP in some brain regions is mediated by AMPA and NMDA receptor trafficking and a direct link between the altered glutamate systems in animals exposed to psychostimulants and dopamine receptor stimulation has recently emerged, I propose to investigate the biochemical mechanisms of ionotropic glutamate trafficking and the role that DA receptors may have in the NAc. Aim 1 will investigate the underlying biochemistry of AMPA receptor trafficking and its acute regulation by DA receptors in acute, naive NAc tissue slices. Since preliminary results have shown increased GluR1 surface expression in rats withdrawn from repeated cocaine exposure, Aim 2 will investigate other possible changes in the surface expression of AMPA, NMDA, and DA receptors in the NAc in this animal model. Our results may describe a mechanistic link between the biochemistry of NAc glutamate receptor trafficking and the neuroplasticty that occurs in drug addiction.

描述（由申请人提供）： 尽管过去十五年的研究为吸毒的神经生物学基础提供了丰富的见解，但整个社会仍然受虐待药物的影响。需要进行更多的研究，以进一步了解与药物成瘾（寻求，渴望和使用复发）相关的持续行为的细胞基础，以帮助提供更好的治疗策略来打击成瘾。我们的假设是成瘾是一种神经元可塑性的一种形式，也许是一种异常的学习形式，在机制上与其他形式的可塑性相似，例如LTD和LTP。该研究建议将提供有关伏隔核（NAC）生化可塑性的重要信息，这是一个对行为动机方面重要的大脑区域，对药物成瘾至关重要。这将进一步了解我们对细胞水平上的瘾相关的适应性的理解。因为某些大脑区域的LTP是由AMPA和NMDA受体运输介导的，并且最近出现了暴露于心理刺激物和多巴胺受体刺激的动物中谷氨酸系统改变的直接联系，我建议研究型谷物谷氨酸的生物化学机制，使谷氨酸的生物化学和该角色的作用纳入DACHONAC。 AIM 1将研究AMPA受体运输的潜在生物化学及其在急性幼稚的NAC组织中DA受体的急性调节。由于初步结果表明，从重复可卡因暴露中撤回的大鼠中GLUR1表面表达增加，AIM 2将研究该动物模型中NAC中AMPA，NMDA和DA受体表面表达的其他可能变化。我们的结果可能描述了NAC谷氨酸受体运输的生物化学与药物成瘾中发生的神经层状之间的机械联系。