Effects of Deep Brain Stimulation on Compulsive Drug Intake

深部脑刺激对强迫性药物摄入的影响

• 批准号: 8249804
• 负责人: George F. Koob
• 金额: $ 21.32万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8249804
• 关键词: Abstinence; Animal Model; Animals; Basal Ganglia; Behavioral; Biological Neural Networks; Brain; Brain Diseases; Brain Mapping; Cerebrum; Chronic; Cocaine; Cocaine Dependence; Cognitive; Cues; Deep Brain Stimulation; Dependence; Development; Disease; Drug Addiction; Drug abuse; Drug usage; Dystonia; Eagles; Frequencies; Funding; Human; Impulsivity; Incentives; Intake; Lesion; Mental disorders; Motivation; Neurobiology; Neurons; Nucleus Accumbens; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Parkinson Disease; Pharmaceutical Preparations; Pharmacological Treatment; Pre-Clinical Model; Process; Rattus; Recruitment Activity; Relapse; Resistance; Rewards; Role; STN stimulation; Stress; Structure; Structure of subthalamic nucleus; Techniques; Testing; Therapeutic; Time; Tremor; addiction; alternative treatment; chronic pain; cocaine relapse prevention; cocaine use; craving; drug abstinence; drug craving; innovation; motivated behavior; motor control; nervous system disorder; neurobiological mechanism; prevent; public health relevance; treatment strategy

DESCRIPTION (provided by applicant: Cocaine addiction is a chronic relapsing disorder in which subjects episodically administer the drug and ultimately transition from nondependent drug use to the compulsive drug use of addiction. A progressive increase in the frequency and intensity of cocaine use, and a high propensity to relapse after abstinence are two of the major behavioral phenomenon that characterizes the development of cocaine addiction. Despite major advances in understanding the neurobiological mechanisms underlying the transition to cocaine dependence, there are no pharmacological treatments for cocaine dependence. Recently, deep brain stimulation of the subthalamic nucleus has been proposed has a surgical strategy for obsessive-compulsive disorders, but it has never been tested in preclinical models of compulsive drug taking and drug seeking. The subthalamic nucleus, a cerebral structure belonging to the basal ganglia and classically associated with motor control, is critically involved in key cognitive processes that become dysfunctional in subjects with drug addiction. The overall objective of this proposal is to use a new, potentially groundbreaking therapeutic approach for the treatment of cocaine addiction using an innovative neurosurgical approach that has shown remarkable results in other brain and mental disorders, associated with highly relevant animal models of compulsive cocaine intake and relapse to cocaine seeking. Preliminary results show that lesion of the subthalamic nucleus limits the escalation of cocaine intake in dependent rats, and that deep brain stimulation of the subthalamic nucleus decreases the motivation for cocaine in rats. Unknown is whether deep brain stimulation of the STN will reverse the escalation of cocaine intake and prevent relapse to cocaine seeking in dependent rats. The specific objectives of this proposal are to determine whether it is possible to reverse the escalation of cocaine (SpA1), and to prevent drug-, stress-, and cue-induced reinstatement to cocaine seeking (SpA2) using deep brain stimulation in the subthalamic nucleus in cocaine dependent rats. These studies will provide new findings on the role of the subthalamic nucleus in the compulsivity associated with cocaine dependence and may open new avenues for the development of innovative treatments of drug addiction in general. PUBLIC HEALTH RELEVANCE: Despite major advances in understanding the neurobiological mechanisms underlying the transition to drug addiction there are no pharmacological treatments available. The overall objective of this proposal is to use new, potentially groundbreaking therapeutic approaches for cocaine addiction using deep brain stimulation of the subthalamic nucleus, associated with highly relevant animal models of compulsive cocaine intake and relapse to cocaine seeking. These studies will provide new findings on the neurobiological substrates of compulsive cocaine taking and craving, have direct translational implications for drug abuse, and may open new avenues for the development of innovative treatments of drug addiction in general.

DESCRIPTION (provided by applicant: Cocaine addiction is a chronic relapsing disorder in which subjects episodically administer the drug and ultimately transition from nondependent drug use to the compulsive drug use of addiction. A progressive increase in the frequency and intensity of cocaine use, and a high propensity to relapse after abstinence are two of the major behavioral phenomenon that characterizes the development of cocaine addiction. Despite major advances in understanding the对可卡因依赖性过渡的基础的神经生物学机制最近没有可卡因的依赖性，对丘脑下核的深度刺激已提出了一种痴迷于强迫症的手术策略。基底神经节和与运动控制的经典相关，与关键认知过程至关重要，这些过程在药物成瘾受试者中变得功能失调。该提案的总体目的是使用一种创新的神经外科手术方法使用一种新的，潜在的突破性治疗方法来治疗可卡因成瘾，该方法在其他大脑和精神疾病中表现出了显着的结果，与高度相关的强迫性可卡因摄入量和对可卡因寻求可卡因相关的动物模型相关。初步结果表明，丘脑下核的病变限制了可卡因在依赖大鼠中的升级，并且对丘脑下核的深脑刺激会降低大鼠可卡因的动机。未知的是，对STN的深脑刺激是否会逆转可卡因摄入的升级，并防止在依赖大鼠中寻求可卡因。该提案的具体目标是确定是否有可能逆转可卡因的升级（SPA1），并防止使用可卡因刺激可卡因刺激可卡因寻求可卡因（SPA2）的药物，应激和提示引起的恢复，可卡因抗Cocaine cocaine cococain cocaine cocaine依赖性大鼠。这些研究将为丘脑核心核在与可卡因依赖性相关的强迫性中的作用提供新的发现，并可能为开发一般的药物成瘾的创新治疗提供新的途径。 公共卫生相关性：尽管在了解过渡到药物成瘾的基础的神经生物学机制方面取得了重大进展，但没有可用的药理治疗。该提案的总体目的是使用对丘脑下核的深度脑刺激可卡因成瘾的新的，潜在的突破性治疗方法，与高度相关的可卡因摄入量和对可卡因寻求可卡因的复发有关。这些研究将提供有关强迫性可卡因服用和渴望的神经生物学底物的新发现，对药物滥用具有直接的翻译意义，并可能为开发一般的药物成瘾的创新治疗提供新的途径。