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

• 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
• 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

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，调节压力的神经递质和 抗压力系统是负强化和成瘾复发的基础。孤啡肽， 与痛敏肽/痛敏FQ肽（NOP）受体相关，是一种这样的神经肽递质， 通过抵消促肾上腺皮质激素释放因子的功能作用发挥其抗应激作用 (CRF)是大脑中主要的压力调节神经肽递质。基本调查 提示CRF和伤害感受素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 延伸杏仁核中的伤害感受素水平是焦虑样行为的原因， 毒瘾复发CRF 1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，以减弱酒精对一系列 成瘾行为因此，制定一种方法来审查通用报告格式是很有意义的。 人类成瘾者的NOP相互作用。在这里，我们将用[11 C]NOP-1A和[11 C] NOP-1B评估健康人。 PET是否氢化可的松诱导的杏仁核CRF增加导致NOP受体改变 约束力该实验将首次记录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 调查事务所 !