MRI of Brain Function and Receptors in Cocaine Addiction

描述：(申请人提供)可卡因成瘾是国民健康问题 有300多万可卡因滥用者需要治疗。这个 这个问题特别隐蔽，因为环境原因导致复发 引发人们对可卡因的“渴望”到目前为止，还没有治疗药物可以预防 可卡因复发。事实上，了解可卡因复发的关键是识别 中枢神经系统的神经解剖学和神经化学机制 助长了暗示引发的渴望。 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。这个多巴胺能系统是 与可卡因相关的神经和行为改变有关 自我管理、戒毒和复职，即对可卡因的渴望。 神经降压素被认为对中皮质边缘具有抑制调节作用 我的意思是。这项提案将调查慢性可卡因的假设 暴露改变脑活动及NT对多巴胺能神经元的调节作用 协助复职。 这项提案中概述的研究将使用功能磁共振 清醒大鼠脑活动变化的磁共振成像(FMRI)研究 可卡因管理和复职。核磁共振也将用于检查 在可卡因自身给药过程中NT结合的特定部位变化， 撤回和复职。利用新开发的顺磁性NT配体，它 可能跟随可卡因相关的NT受体的变化 动物在几个星期内。有了这种重复的“体内放射自显影”，它是 可能将可卡因相关大脑活动的变化与 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.