Evaluation of Neuropeptide Y as a Target for Cocaine-Dependence Treatment

神经肽 Y 作为可卡因依赖治疗靶点的评估

• 批准号: 7479707
• 负责人: Alexis Cassandra Thompson
• 金额: $ 29.83万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479707
• 关键词: Abstinence; Affective; Agonist; Animal Model; Anxiety; Behavior; Brain; Characteristics; Cocaine; Cocaine Dependence; Communicable Diseases; Communities; Condition; Crime; Cues; Daily; Dependence; Development; Drug Delivery Systems; Drug Design; Drug Exposure; Economics; Effectiveness; Environment; Evaluation; Exposure to; Extinction (Psychology); Felis catus; Individual; Injection of therapeutic agent; Lead; Measures; Mental Depression; Neonatal; Neuraxis; Neurobiology; Neurotransmitters; Pharmaceutical Preparations; Pharmacotherapy; Purpose; Range; Rattus; Recording of previous events; Relapse; Research; Social Interaction; Social Problems; Stress; Symptoms; System; Testing; Training; Treatment outcome; Week; Withdrawal; craving; design; disturbance in affect; driving behavior; improved; neuropeptide Y; neurotransmission; preference

DESCRIPTION (provided by applicant): Cocaine use and dependence exact a considerable toll, not only to the individual user, but also to the community at large because the cocaine-driven behavior of the user causes a wide range of economic, biomedical and social problems, including crime, spread of infectious disease, and neonatal drug exposure. Currently there are no recommended drug therapies for cocaine dependence, although the need is great. Functional characteristics of the neurotransmitter neuropeptide Y (NPY) suggest that the development of medicinal drugs that target NPY neurotransmission will be effective in reducing cocaine craving and mood disturbances during periods of abstinence. Craving, anxiety, and depression during periods of cocaine abstinence underlie relapse. The research proposed here will test the effectiveness of NPY agonists (drugs that stimulate NPY activity) to reduce craving and heightened anxiety that occur during short (1 week) and long (3 week) periods of abstinence from cocaine in an animal model of cocaine dependence. To assess craving, rats will be tested in a place preference apparatus in which they will be trained to associate a particular place (a neutral environment) with a daily cocaine treatment. During periods of cocaine abstinence, the rat's preference to go to and remain in the place they previously received cocaine ("the neutral environment") will provide an indirect measure of cocaine seeking (craving). The effect of increasing NPY activity in the brain during periods of cocaine abstinence on place preference will be used to assess the effect of NPY on cue-induced cocaine seeking. Additionally, the interaction between NPY and a predator stress (exposure to a cat-scented cloth) on place preference, or the interaction between NPY and a subsequent exposure to cocaine on place preference, will be assessed to determine if NPY blocks stressand drug-induced increases in cocaine seeking. Finally, the impact of NPY on cocaine withdrawal will be assessed by evaluating the ability of NPY to suppress the heightened anxiety associated with the first 48 hrs of abstinence. The results will add to our understanding of the neurobiological substrates that underlie cocaine dependence and indicate whether or not the pursuit of medicinal compounds that target NPY neurotransmission is warranted for the purpose of managing cocaine dependence.

描述（由申请人提供）：可卡因的使用和依赖性确切的损失不仅对个人用户，而且对整个社区的损失，因为用户的可卡因驱动的行为会导致广泛的经济，生物医学和社会问题，包括犯罪，包括感染性疾病的传播以及新生儿药物的暴露。目前，尚无针对可卡因依赖的药物疗法，尽管需求很大。神经递质神经肽Y（NPY）的功能特征表明，靶向NPY神经传递的药物的开发将有效减少可卡因的渴望和戒酒时期。在可卡因戒酒期间，渴望，焦虑和抑郁症是复发的基础。此处提出的研究将测试NPY激动剂（刺激NPY活性的药物），以减少渴望和焦虑症，并在短期（1周）和长期（3周）期间发生可卡因在可卡因依赖性动物模型中禁止可卡因。为了评估渴望，将在一个地点偏好设备中对大鼠进行测试，在该设备中，他们将接受培训以将特定位置（中性环境）与每日可卡因治疗相关联。在可卡因禁欲期间，大鼠偏爱去并留在他们先前接受的可卡因的地方（“中性环境”）将提供间接的可卡因寻求（渴望）。可卡因禁欲期间，大脑中NPY活性增加对位置偏好的影响将用于评估NPY对提示引起的可卡因寻求的影响。此外，将评估NPY与捕食者应力（暴露于猫味的布）之间的相互作用，或者将评估NPY与随后接触可卡因的相互作用，以确定NPY是否会阻止NPY阻止压力和药物诱导的可卡因寻求增加。最后，通过评估NPY抑制与禁欲的前48小时相关的焦虑的能力来评估NPY对可卡因戒断的影响。结果将增加我们对可卡因依赖性基础的神经生物学底物的理解，并表明是否有必要追求针对NPY神经传递的药用化合物，以便管理可卡因依赖性。