Dopamine D2/D3 Receptors in Compulsive Disorders

强迫症中的多巴胺 D2/D3 受体

• 批准号: 7935212
• 负责人: james H Woods
• 金额: $ 46.62万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7935212
• 关键词: Agonist; Animal Model; Behavior; Behavior Therapy; Behavioral; Behavioral Model; Cocaine; Data; Disease; Dopamine; Dopamine Agonists; Dopamine Receptor; Eating; Elements; Evaluation; Exercise; Gambling; Goals; Home environment; Individual; Intervention; Modeling; Nature; Obsessive compulsive behavior; Operant Conditioning; Organism; Pharmaceutical Preparations; Pharmacological Treatment; Positioning Attribute; Prevention approach; Procedures; Process; Psychopathology; Quinpirole; RNA Interference; Rattus; Research; Respondent; Rodent; Role; Sex Behavior; Stimulus; Testing; Thinking; Time; Water; behavioral pharmacology; chemical synthesis; conditioning; design; excessive behavior; neurochemistry; programs; public health relevance; receptor; reinforced behavior; reinforcer; sex; therapy development

DESCRIPTION (provided by applicant): Compulsive behaviors, including excessive eating, gambling, shopping, exercising, or drug-taking, can develop over time in individuals without other psychopathology. Although compulsive behavior is marked by excessive engagement in a particular behavior, animal models of compulsive behavior suggest that another defining feature is behavior that is disconnected from reinforcer delivery. Thus, people may gamble compulsively even though they do not win often, or shop excessively even when they may not use what they have purchased. Our hypothesis is that these types of reinforcer- disconnected behaviors result when both operant (instrumental, goal-tracking) and respondent (Pavlovian, classical, sign-tracking) conditioning processes converge on the same behavior. In addition, individuals must be sensitized to dopamine, and the compulsive behavior is more likely to occur in the presence of a D3/D2 agonist acting on the sensitized dopamine receptors. We will test this hypothesis in three behavioral models: 1) quinpirole-induced responding for stimuli associated with cocaine; 2) quinpirole-induced responding for water in the presence of water; and 3) quinpirole as an occasion setter for either cocaine or water-reinforced behavior. The behavioral pharmacology of these models will be tested with various dopamine agonists and antagonists, and the roles of sensitization, goal-tracking, and sign-tracking will be studied. Understanding the environmental, behavioral, neurochemical, and pharmacological aspects of compulsive disorders will hopefully contribute to the development of treatments for these debilitating disorders. PUBLIC HEALTH RELEVANCE: The purpose of this proposal is to determine various environmental and neurochemical contributors to compulsive behavior (e.g., excessive gambling, shopping, eating, sexual behavior, and drug-taking). Our hypothesis, that compulsions result when the same classically conditioned and operantly conditioned behavior is established in the presence of sensitized dopamine receptors and stimulation of dopamine receptors, will be tested in three rat models in this research effort. Evaluation of the ability of selective dopamine receptors, as well as silencing the RNA for the D3 receptor, to modify the compulsive behavior should help point towards possible pharmacological treatment of these disorders, and understanding of the setting conditions will suggest behavioral therapy and prevention approaches.

描述（由申请人提供）：强迫行为，包括过度饮食，赌博，购物，锻炼或吸毒，可以随着时间的流逝而在没有其他心理病理学的个人中发展。尽管强迫性行为以特定行为的过度参与为特征，但强迫行为的动物模型表明，另一个定义特征是与加强剂传递断开连接的行为。因此，即使人们不经常获胜，也可能会强迫赌博，或者即使可能不使用自己购买的商品，他们也会过度购物。我们的假设是，当操作者（工具，目标跟踪）和受访者（Pavlovian，Pavlovian，经典，签名）调理过程都会融合相同的行为时，这些类型的增强器断开行为会产生。另外，必须将个体敏感到多巴胺，并且在作用于敏化多巴胺受体的D3/D2激动剂存在下，强迫性行为更有可能发生。我们将在三个行为模型中检验这一假设：1）奎因螺氏诱导的与可卡因相关的刺激的反应； 2）在水存在下，奎因螺染引起的水反应； 3）作为可卡因或强力行为的Quinpipole作为场合。这些模型的行为药理学将与各种多巴胺激动剂和拮抗剂一起测试，并将研究致敏，目标跟踪和标志跟踪的作用。了解强迫症的环境，行为，神经化学和药理方面，有望有助于为这些令人衰弱的疾病的治疗发展。公共卫生相关性：该提案的目的是确定强迫行为的各种环境和神经化学贡献者（例如，过多的赌博，购物，饮食，性行为和吸毒）。我们的假设是，在这项研究工作中，将在三个大鼠模型中测试，在存在敏化多巴胺受体的情况下建立相同的经典条件和操作的行为并刺激多巴胺受体的刺激。评估选择性多巴胺受体的能力，以及对D3受体的RNA进行沉默，以修改强迫性行为，应有助于指出可能对这些疾病的药理学治疗，对设置条件的了解将暗示行为治疗和预防方法。