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Multimodal Neuroimaging x Optogenetics: A Novel Approach to Study Reward Processing Under Pathological Conditions

多模态神经影像 x 光遗传学：一种研究病理条件下奖励处理的新方法

基本信息

批准号：
174466612
负责人：
Professor Dr. Rainer Spanagel
金额：
--
依托单位：
Abteilung Psychopharmakologie
依托单位国家：
德国
项目类别：
Reinhart Koselleck Projects
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/174466612?language=en
关键词：
Multimodal Neuroimaging Optogenetics Novel Approach

项目摘要

Background: Midbrain dopamine neurons play a key role in reward processing and subsequent goaldirected behaviour. Altered dopaminergic activity and dysfunctional reward processing occurs in several psychiatric disorders. Especially in drug addiction goal-directed behaviour is severely impaired, as the behavioural activities of a drug addict become increasingly drug-oriented at the expense of all other daily activities. The underlying neurobiology of altered reward processing during the development, maintenance, and possible remission of an addicted behaviour is poorly understood. Goa/s.'To study the dynamics of midbrain dopamine neurons and their connectivity within the reward system by multimodal 9.4T magnetic resonance imaging (MRI) in rats that show addictive-like behaviour. Following a prolonged period of intravenous cocaine self-administration approx. 15% of rats develop addictive-like behaviour similar to that seen in human cocaine users diagnosed as addicts. Using this animal model, alterations in reward processing and underlying dopaminergic activity and connectivity will be studied longitudinally by means of repeated multimodal MRI in animals that become addicted versus animals that show resilience to addictive behaviour.Outcome.'These studies will provide fundamental new insights into reward processing and underlyingalterations in dopaminergic function and connectivity in the context of addictive behaviour. Given thatoutcome measures from experimental animals will be derived from neuroimaging studies the findingswill be directly translatable to the human condition and will dramatically impact on our knowledge ofdrug addiction, pathological gambling, depression, and several other psychiatric disorders.

背景：中脑多巴胺神经元在奖励处理和随后的目标导向行为中起关键作用。多巴胺能活动改变和奖励处理功能障碍发生在几种精神疾病中。特别是在吸毒成瘾中，以目标为导向的行为受到严重损害，因为吸毒成瘾者的行为活动越来越以毒品为导向，而牺牲了所有其他日常活动。在成瘾行为的发展、维持和可能的缓解过程中，奖赏处理改变的潜在神经生物学机制尚不清楚。果阿/ s。“通过多模态9.4T磁共振成像（MRI）研究表现出成瘾行为的大鼠中脑多巴胺神经元的动态及其在奖励系统中的连通性。”在长时间静脉注射可卡因后。15%的老鼠表现出类似于被诊断为成瘾的人类可卡因使用者的成瘾行为。使用这种动物模型，将通过重复的多模态MRI对成瘾动物和对成瘾行为表现出弹性的动物进行纵向研究，研究奖励处理和潜在多巴胺能活动和连通性的变化。“这些研究将为奖励处理和多巴胺功能的潜在变化以及成瘾行为背景下的连接提供基本的新见解。”考虑到实验动物的结果测量将来源于神经成像研究，这些发现将直接转化为人类状况，并将极大地影响我们对药物成瘾、病理性赌博、抑郁症和其他几种精神疾病的认识。