BRAIN SUBSTRATES OF POSITIVE REINFORCEMENT

正强化的大脑基质

• 批准号: 2120498
• 负责人: AARON ETTENBERG
• 金额: $ 12.01万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120498
• 关键词: behavior test; brain electronic stimulator; brain metabolism; dopamine; dopamine agonists; dopamine antagonists; dopamine receptor; electronic stimulator; haloperidol; laboratory rat; limbic system; motivation; neuropharmacology; operant conditionings; pimozide; psychomotor function; reinforcer; self stimulation; sweetening agents

A primary hypothesis about the brain mechanisms through which drugs of abuse producing their reinforcing effects, is that such agents act on endogenous brain reward substrates whose "natural" function is to ensure the incentive value of biologically essential stimuli such as food and water. Thus, understanding the brain mechanisms through which natural reinforcers act, should be relevant to our understanding of how drugs of abuse act in their role as positive reinforcers. In this regard, our laboratory has been involved in studies of the behavioral function of central dopaminergic pathways for several years. More specifically, the present proposal is intended to build upon our recent findings with dopamine (DA) receptor antagonist drugs. The administration of such drugs has long been known to interfere with the performance of operant behaviors in laboratory animals. However, interest and controversy continue to exist regarding the precise mechanism(s) through which these drugs exert their behavioral effects. We have made considerable progress establishing both limbic (reward) and extrapyramidal (motoric) deficits in DA antagonist-treated animals using a series of novel carefully- controlled behavioral test procedures developed in our laboratory. The novelty of our reinforcement assays is that they permit the investigation of drug-induced reward deficits at a test-time when the drug under investigation is no longer active. this obviously increases the power of our data set since non-specific performance consequences of drug administration are not present on test day. In the proposed experiments we plan to employ our behavioral tests in three specific ways: 1) to assess the relative contributions of D1 and D2 dopamine receptor subtypes to the behavioral deficits observed during DA antagonist challenge; 2) to extend the investigation of DA antagonist effects to a variety of positive reinforcers; and 3) to identify the brain sites responsible for the behavioral actions of DA antagonist drugs. Together, the proposed experiments should provide important new information on a) the precise mechanisms through which such drugs exert their behavioral effects; and b) the nature of the role of central dopaminergic neurons in reward and motivational processes. It is our view that such information will prove valuable to investigations of the neural substrates through which drugs of abuse exert their reinforcing actions.

一个关于药物通过大脑机制的初步假设， 滥用产生其强化作用的原因是，这些药物作用于 内源性大脑奖励底物，其“自然”功能是确保 生物学上必要的刺激物，如食物和 水 因此，了解大脑机制，通过自然 毒品的行为，应该与我们对毒品的认识有关。 虐待行为在他们的角色作为积极的补充剂。 在这方面， 实验室已经参与了行为功能的研究， 中枢多巴胺能神经通路的研究 更具体而言是 目前的建议旨在建立在我们最近的调查结果， 多巴胺（DA）受体拮抗剂药物。 给予这类 长期以来，药物一直被认为会干扰操作性的表现。 实验室动物的行为。 然而，兴趣和争议 关于这些问题的确切机制， 药物发挥其行为效应。 我们已经取得了相当大的进展 建立边缘系统（奖励）和锥体外系（运动）缺陷 在DA拮抗剂治疗的动物中，使用一系列新的仔细- 我们实验室开发的受控行为测试程序。 的 我们的强化分析的新奇在于，它们允许调查 药物诱导的奖励赤字在测试时间，当药物 调查不再活跃。 这显然增加了 由于药物的非特异性性能后果， 在测试日不存在给药。 在拟议的实验中， 我们计划在三个具体方面使用我们的行为测试：1） 评估D1和D2多巴胺受体亚型的相对贡献 DA拮抗剂激发期间观察到的行为缺陷; 2） 为了将DA拮抗剂作用的研究扩展到各种 阳性反应物; 3）确定负责 DA拮抗剂药物的行为作用。 在一起，拟议的 实验应该提供重要的新信息a）精确的 这些药物发挥其行为效应的机制;以及 B）中枢多巴胺能神经元在奖赏中的作用的性质， 动机过程。 我们认为这些信息将证明 对研究药物通过的神经基质很有价值 滥用的行为会产生强化作用。