Benzodiazepine Modulation of Opiate Reward

描述：（申请人提供） 本项目建议研究以下假设的增强效应： 苯二氮卓类药物（BDZ）预处理对静脉阿片类药物奖励的影响。临床 案例研究报告了许多明显的阿片类药物 用口服BDZ镇静剂自我镇静的阿片类药物滥用者的增强 在注射鸦片之前在我们的实验室里，我们已经能够 证实了BDZ-阿片类药物在大鼠中的奖励相互作用。我们的初步结果 已经证明了海洛因诱导的大小的可靠增强 优先选择用低剂量BDZ、阿普唑仑预处理的动物; 该作用被BDZ受体拮抗剂治疗阻断， 氟马西尼。最大的效果是在低剂量的海洛因和 阿普唑仑单独给药时不产生药物奖励的证据。 目前的建议以两个具体的形式建立在这些结果的基础上。 目的：1）通过测试 丁螺环酮（一种非BDZ抗焦虑药）促进阿片奖赏的能力 并研究BDZ-阿片与其他药物的相互作用 奖励（即，操作性自我给药）;和2）识别（使用受体 拮抗剂微量输注到离散的脑区域）的关键部位， 中枢神经系统可能是BDZ-阿片相互作用的基础。这项工作将 这是第一次对这种现象进行系统的动物研究， 阐明BDZ-阿片相互作用的确切性质和机制。

DESCRIPTION: (provided by the applicant) The present project proposes to examine the putative enhancing effects of benzodiazepine (BDZ) pretreatment on intravenous opiate drug reward. Clinical case studies have reported numerous examples of apparent opiate drug enhancement in opiate abusers who self-medicate with an oral BDZ tranquilizer prior to their opiate injection. In our laboratory, we have been able to confirm this BDZ-opiate reward interaction in rats. Our preliminary results have demonstrated a reliable potentiation in the size of the heroin-induced place preferences in animals pretreated with low doses of the BDZ, alprazolam; an effect which is blocked by treatment with the BDZ receptor antagonist, flumazenil. The maximal effect is produced at low doses of both heroin and alprazolam that do not produce evidence of drug reward when administered alone. The current proposal builds upon these results in the form of two specific aims: 1) to replicate and extend the preliminary findings by testing the ability of buspirone (a non-BDZ anxiolytic agent) to facilitate opiate reward and to investigate the BDZ-opiate interaction with other measures of drug reward (i.e., operant self-administration); and 2) to identify (using receptor antagonist microinfusions into discrete brain regions) the critical sites in the CNS that might underlie this BDZ-opiate interaction. This work would represent the first systematic animal research on this phenomena and help to elucidate the precise nature and mechanisms underlying BDZ-opiate interactions.