MRI of Brain Function and Receptors in Cocaine Addiction

描述：（由申请人提供）可卡因成瘾是一个国家的健康 超过300万可卡因滥用者需要治疗。的 问题是特别阴险的，因为复发，由于环境 唤起了对可卡因的渴望到目前为止，还没有治疗药物可以预防 可卡因复吸事实上，理解可卡因复吸的关键是识别 中枢神经系统的神经解剖学和神经化学机制 导致了线索诱发的渴望 神经降压素（NT）是一种与中枢神经系统密切相关的神经肽 多巴胺能中皮质边缘系统这个多巴胺能系统 与可卡因相关的神经和行为变化有关 自我给药、戒断和恢复，即可卡因渴望。 神经降压素被认为对中脑皮质边缘神经元的活动具有抑制性调节作用。 Thnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn这项提案将调查慢性可卡因 暴露改变脑活动和NT对多巴胺能的调节作用 促进恢复。 在这项建议中概述的研究将使用功能磁共振 在清醒大鼠中进行功能磁共振成像（fMRI），以研究大脑活动的变化， 可卡因管理和恢复。MRI也将用于检查 可卡因自身给药期间NT结合的位点特异性变化， 撤销和恢复。与新开发的顺磁性NT配体， 可能在相同的神经元中追踪与可卡因相关的NT受体变化， 动物在几周内。通过这种重复的“体内放射自显影”， 可能将可卡因相关的大脑活动的变化与 中皮质边缘系统中NT结合的离散变化。

DESCRIPTION: (provided by applicant) Cocaine addiction is a national health problem with over three million cocaine abusers in need of treatment. The problem is particularly insidious because of the relapse due to environmentally evoked cocaine 'craving.' To date there are no therapeutic agents to prevent cocaine relapse. Indeed the key to understanding cocaine relapse is identifying the neuroanatomyand neuro chemical mechanisms in the central nervous system contributing to cue-evoked craving. Neurotensin (NT) is a neuropeptide in the central nervous system closely linked to the dopaminergic mesocorticolimbic system. This dopaminergic system is involved in the neurological and behavioral changes associated with cocaine self-administration, withdrawal and reinstatement, i.e. cocaine craving. Neurotensin is thought to exert an inhibitory regulation on mesocorticolimbic thnction. This proposal will investigate the hypothesis that chronic cocaine exposure alters brain activity and NT's regulatory role on doparninergic facilitation of reinstatement. The studies outlined in this proposal will use functional magnetic resonance imaging (fMRI) in conscious rats to study changes in brain activity with cocaine administration and reinstatement. MRI will also be used to examine site-specific changes in NT binding during cocaine self-administration, withdrawal and reinstatement. With a newly developed paramagnetic NT ligand, it is possible to follow cocaine-associated changes in NT receptors in the same animals over several weeks. With this repeated 'in vivo autoradiography,' it is possible to correlate changes in cocaine associated brain activity with discrete changes in NT binding in the mesocorticolimbic system.