GABA Modulation of Cocaine & Heroin Self-Administration

描述：可卡因成瘾仍然是一个严重的医学问题 社会和经济成本。那些寻求治疗成瘾的人发现了它 戒除精神刺激剂和复吸毒品极其困难 采取行动是常态。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 影响吸毒和复发。我们期待着更清楚地了解 这些基本的大脑机制将在药物的开发中有用 这可以有效地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 对可卡因强化的特殊作用。将使用几种型号来 评估巴氯芬抗可卡因作用的有效性和特异性。我们 先前已经表明，巴氯芬和其他GABAB激动剂具有强大的 对可卡因自身给药有明显的特异性影响。初步 临床数据(由其他人报告)也令人鼓舞。为了努力 描述这种效应的药理特异性，我们将 GABAB拮抗剂CGP56433是否减弱巴氯芬诱导的 抑制可卡因的摄入。另一个目的是确定(S)的遗址 GABA对可卡因强化的调节作用。的影响 可卡因限定脑区微量注射巴氯芬 自我管理行为和其他绩效衡量标准将 评估过了。累进比率表和其他程序，旨在评估 将使用可卡因增强功效的变化。我们最近做了 开发了一种产生狂欢型可卡因模式的程序 大鼠的自我给药。实验将检验各种不同的 巴氯芬在这种晚期成瘾模型中的治疗方案。这个 注射巴氯芬或脑内注射对海洛因的影响程度 还将对自治进行评估。

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.