Effects of the combination of metyrapone and oxazepam on intravenous nicotine self-administration in rats.
Effects of the combination of metyrapone and oxazepam on intravenous nicotine self-administration in rats.
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DOI：
10.1007/s00213-012-2682-4
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发表时间：
2012-09
影响因子：
3.4
通讯作者：
Koob, George F.
中科院分区：
文献类型：
--
作者：
Goeders, Nicholas E.;Cohen, Ami;Fox, Barbara S.;Azar, Marc R.;George, Olivier;Koob, George F.
关键词：
尽管增加了关于其危险性的教育，但吸烟仍然是一个重大的公共卫生问题，因为吸烟会导致严重的相关健康后果，如癌症、呼吸道疾病和心血管疾病。大多数吸烟者在尝试戒烟时失败，目前的药理学干预措施的疗效水平相对较低，并与显著的不良事件相关。我们以前曾报道过，甲吡酮和奥沙西泮的组合，在剂量是无效的单独交付时，导致剂量相关的减少可卡因自我管理的大鼠，而不影响食物维持在同一会话期间的反应。本研究旨在检测甲吡酮：奥沙西泮组合给药对大鼠尼古丁自我给药的影响。在接受训练的大鼠中测试了甲吡酮（12.5、25或50 mg/kg）和奥沙西泮（5或10 mg/kg）的几种剂量组合，以在1小时自我给药期间使用固定比例和递增比例（PR）强化方案静脉内（IV）自我给药尼古丁（0.03 mg/kg/输注）。低剂量甲吡酮和奥沙西泮联合给药显著降低了大鼠IV尼古丁自我给药。在12.5 mg/kg甲吡酮和5 mg/kg奥沙西泮的最低剂量下，单独使用药物不会减少IV尼古丁自我给药，但联合用药有效。伐尼克兰也使用固定比例的时间表进行了测试，尼古丁摄入量的减少与中等剂量的组合相似。本研究的结果表明，甲吡酮和奥沙西泮的组合用于人类戒烟的潜在效用。
Despite increased education regarding its dangers, cigarette smoking remains a significant public health concern due to serious associated health consequences such as cancer and respiratory and cardiovascular diseases. Most smokers fail in their attempts to quit smoking, and current pharmacological interventions have relatively low levels of efficacy and are associated with significant adverse events. We have previously reported that combinations of metyrapone and oxazepam, administered at doses that were ineffective when delivered singly, resulted in dose-related decreases in cocaine self-administration in rats while not affecting food-maintained responding during the same sessions. The current study was designed to test the effects of the administration of a metyrapone:oxazepam combination on nicotine self-administration in rats. Several dose combinations of metyrapone (12.5, 25 or 50 mg/kg) and oxazepam (5 or 10 mg/kg) were tested in rats trained to intravenously (IV) self-administer nicotine (0.03 mg/kg/infusion) during 1-h self-administration sessions using both fixed-ratio and progressive-ratio (PR) schedules of reinforcement. The administration of low doses of metyrapone and oxazepam in combination significantly decreased IV nicotine self-administration in rats. At the lowest doses of 12.5 mg/kg of metyrapone and 5 mg/kg of oxazepam, the drugs alone did not decrease IV nicotine self-administration, but the combination was effective. Varenicline was also tested using the fixed-ratio schedule, and reductions in nicotine intake were similar to those seen with the moderate dose of the combination. The results of this study suggest a potential utility of the combination of metyrapone and oxazepam for smoking cessation in humans.
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DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
22.4
作者：
Kassel, JD;Stroud, LR;Paronis, CA
通讯作者：
Paronis, CA
影响因子：
4.2
作者：
Goeders, NE;Peltier, RL;Guerin, GF
通讯作者：
Guerin, GF
影响因子：
3.7
作者：
Caggiula, AR;Donny, EC;Perkins, KA
通讯作者：
Perkins, KA
影响因子：
2.9
作者：
Goeders, NE;Guerin, GF
通讯作者：
Guerin, GF