GABA Modulation of Cocaine & Heroin Self-Administration

GABA 对可卡因的调节

• 批准号: 6634287
• 负责人: David Charles Stephen Roberts
• 金额: $ 21.6万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-10 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634287
• 关键词: GABA receptor; cocaine; craving; heroin; laboratory rat; muscle relaxants; neurobiology; neurotransmitter agonist; neurotransmitter metabolism; substance abuse related behavior

DESCRIPTION: Cocaine addiction continues to be a medical problem with profound social and financial cost. Those seeking treatment for their addiction find it extremely difficult to abstain from psychostimulant use and relapse to drug taking behavior is the norm. Our long term objective is to understand the neurobiology of cocaine abuse and define the neurotransmitter interactions that influence drug taking and relapse. We expect that a clearer understanding of these basic brain mechanisms will be useful in the development of a medication that could effectively suppress cravings for cocaine. Our working hypothesis is that drugs which act specifically at GABA synapses produce behaviorally specific effects on cocaine reinforcement. Several models will be used to assess the efficacy and specificity of the anti-cocaine effects of baclofen. We have previously shown that baclofen and other GABAB agonists have powerful and apparently specific effects on cocaine self-administration in rats. Preliminary clinical data (reported by others) have also been encouraging. In an effort to characterize the pharmacological specificity of this effect, we will investigate whether the GABAB antagonist CGP56433 attenuates baclofen-induced suppression of cocaine intake. A further aim is to identify the site(s) of action of the GABA modulation of cocaine reinforcement. The effects of microinjections of baclofen into defined brain areas on cocaine self-administration behavior and other measures of performance will be assessed. A progressive ratio schedule and other procedures designed to assess changes in the reinforcing efficacy of cocaine will be used. We have recently developed a procedure that produces binge-type patterns of cocaine self-administration in the rat. Experiments will examine the effect of various treatment regimens of baclofen in this model of late stage addiction. The degree to which either IP or intracerebral injections of baclofen affect heroin self-administration will also be assessed.

描述：可卡因成瘾仍然是一个影响深远的医学问题 社会和财​​务成本。那些寻求治疗毒瘾的人找到了它 戒除精神兴奋剂的使用和吸毒极其困难 采取行为是常态。我们的长期目标是了解 可卡因滥用的神经生物学并定义神经递质相互作用 影响吸毒和复吸。我们期望能有更清晰的认识 这些基本的大脑机制将有助于药物的开发 这可以有效抑制对可卡因的渴望。我们的工作假设是 专门作用于 GABA 突触的药物会产生行为 对可卡因强化的具体影响。多个模型将用于 评估巴氯芬抗可卡因作用的功效和特异性。我们 先前已表明巴氯芬和其他 GABAB 激动剂具有强大且 对大鼠可卡因自我给药有明显的特异性影响。初步的 临床数据（其他人报告的）也令人鼓舞。努力 描述这种作用的药理学特异性，我们将 研究 GABAB 拮抗剂 CGP56433 是否减弱巴氯芬诱导的 抑制可卡因摄入。进一步的目标是确定 GABA 调节可卡因强化的作用。的影响 将巴氯芬显微注射到可卡因的特定大脑区域 自我管理行为和其他绩效衡量标准将 评估。渐进比率表和其他旨在评估的程序 将使用可卡因增强功效的变化。我们最近有 开发了一种产生可卡因暴饮型模式的程序 大鼠自我给药。实验将检验各种效果 巴氯芬在这种晚期成瘾模型中的治疗方案。这 腹腔注射或脑内注射巴氯芬对海洛因的影响程度 自我管理也将受到评估。