In vivo imaging of corticotropin releasing factor-nociceptin receptor interactions

促肾上腺皮质激素释放因子-伤害感受肽受体相互作用的体内成像

基本信息

批准号：
9198085
负责人：
RAJESH NARENDRAN
金额：
$ 19.52万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9198085
关键词：
Abstinence Addictive Behavior Agonist Alcohol consumption Alcoholism Alcohols Amygdaloid structure Animal Model Binding Blood Blood - brain barrier anatomy Brain Brain imaging CRF receptor type 1 CRH gene Cell Nucleus Chronic Disease Compulsive Behavior Corticotropin-Releasing Hormone Cues Data Dopamine Dynorphins Female Future Gender Glucocorticoid Receptor Human Hydrocortisone Image Impulsive Behavior Injection of therapeutic agent Intoxication Intravenous Investigation Lateral Link Literature Measures Mediating Mental disorders Methodology Microdialysis Negative Reinforcements Neuropeptides Neurotransmitters Norepinephrine Nucleus Accumbens Peptide Receptor Peptides Phase Positive Reinforcements Positron-Emission Tomography Relapse Rodent Role Self Administration Sheep Staging Stress Structure of terminal stria nuclei of preoptic region System Testing Time Validation Vasopressins Withdrawal Withdrawal Symptom addiction alcohol effect alcohol reward anxiety-like behavior cooking craving gamma-Aminobutyric Acid human subject hypocretin in vivo in vivo imaging interest intravenous administration motivated behavior neuropeptide Y nociceptin nociceptin receptor novel therapeutics preference radiotracer receptor binding receptor expression research study theories transmission process

项目摘要

Basic investigations postulate that an imbalance between neurotransmitters regulating the stress and anti-stress systems underlie negative reinforcement and relapse in addiction. Nociceptin, which binds to the nociceptin/orphanin FQ peptide (NOP) receptor, is one such neuropeptide transmitter that exerts its anti-stress effects by counteracting the functional effects of corticotropin releasing factor (CRF), the primary stress-mediating neuropeptide transmitter in the brain. Basic investigations suggest that CRF and nociceptin facilitate and inhibit anxiety-like behaviors respectively. Convergent with this is data from animal models of alcoholism that support increased CRF and decreased nociceptin levels in the extended amygdala as the reason for anxiety-like behaviors that underlie relapse in addiction. This postulation is further supported by the ability of CRF1 receptor antagonists and NOP receptor agonists to blunt the reinforcing and motivational effects of alcohol on a range of addictive behaviors. Thus, it is of considerable interest to develop a methodology to examine CRF- NOP interactions in human addicts. Here, we will evaluate in healthy humans with [11C]NOP-1A and PET whether hydrocortisone-induced increases in amygdala CRF leads to altered NOP receptor binding. This experiment will for the first time document an in vivo interaction between CRF and NOP, and set the stage for evaluating whether this interaction is abnormal in addiction in future investigations. !

基础研究假设调节压力和调节神经递质之间的不平衡抗压力系统是负强化和成瘾复发的基础。伤害感受肽，结合伤害感受肽/孤啡肽 FQ 肽 (NOP) 受体是这样一种神经肽递质通过抵消促肾上腺皮质激素释放因子的功能作用来发挥抗应激作用（CRF），大脑中主要的压力介导神经肽递质。基础调查表明 CRF 和伤害感受肽分别促进和抑制焦虑样行为。收敛这是来自酗酒动物模型的数据，支持 CRF 增加和减少扩展杏仁核中的伤害感受肽水平是导致焦虑样行为的原因毒瘾复发。 CRF1 受体拮抗剂的能力进一步支持了这一假设和 NOP 受体激动剂可减弱酒精对一系列疾病的强化和激励作用成瘾行为。因此，开发一种检查 CRF 的方法非常有意义。 NOP 与人类成瘾者的相互作用。在这里，我们将使用 [11C]NOP-1A 和 PET 氢化可的松诱导的杏仁核 CRF 增加是否会导致 NOP 受体改变绑定。该实验将首次记录 CRF 和 NOP 之间的体内相互作用，并为将来评估这种相互作用在成瘾中是否异常奠定基础调查。！