GABA Modulation of Cocaine & Heroin Self-Administration

可卡因成瘾仍然是一个医学问题， 社会和财政成本。那些寻求治疗成瘾的人发现， 极难戒除精神兴奋剂和复吸 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，并定义神经递质的相互作用， 影响吸毒和复吸。我们希望， 这些基本的大脑机制将有助于药物的开发 能有效抑制对可卡因的渴望我们的假设是 这种药物专门作用于GABA突触， 对可卡因强化的具体影响。几种模型将用于 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， 对大鼠可卡因自我给药的明显特异性作用。初步 临床数据（其他人报告的）也令人鼓舞。为了努力 描述这种作用的药理学特异性，我们将 研究GABAB拮抗剂CGP 56433是否能减弱Bacterium诱导的 抑制可卡因的摄入。另一个目的是确定 GABA对可卡因强化的调节作用。的影响 将巴氯芬微量注射到可卡因的特定脑区 自我管理行为和其他绩效指标将被 评估。累进比率表和其他程序旨在评估 将使用可卡因增强效力的变化。我们最近 开发了一种程序， 大鼠自我给药。实验将检查各种 巴氯芬的治疗方案。的 IP或脑内注射巴氯芬对海洛因的影响程度 还将评估自我管理。

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.