...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Experimental and clinical psychopharmacology >Rapid Nicotine Tolerance and Cross-Tolerance to Varenicline in Rhesus Monkeys: Drug Discrimination
【24h】

Rapid Nicotine Tolerance and Cross-Tolerance to Varenicline in Rhesus Monkeys: Drug Discrimination

机译：在恒河猴中快速尼古丁耐受性和交叉耐受性：药物歧视

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Acute tolerance to effects of nicotine plays an important role in nicotine dependence, but the mechanism underlying these effects is unclear. Drug discrimination was used in the current study to examine the impact of nicotine pretreatment on sensitivity to the discriminative stimulus effects of nicotine and the FDA-approved smoking cessation pharmacotherapy varenicline. Rhesus monkeys (n = 4) discriminated 0.032 mg/kg nicotine base iv from saline under an FR5 schedule of stimulus-shock termination. Both nicotine and varenicline increased drug-appropriate responding; ED50 values (95% confidence limits) were 0.0087 [0.0025, 0.030] and 0.028 [0.0096, 0.082] mg/kg, respectively. Additional pretreatment injections of the training dose of nicotine (0.032 mg/kg, iv) produced tolerance to its discriminative stimulus effects and the magnitude of this effect was related to the number of pretreatment injections administered. Two pretreatment injections of the training dose of nicotine (0.032 mg/kg, iv) produced a 5.4-fold rightward shift in the nicotine dose-response function and a sevenfold rightward shift in the varenicline dose-response function. The duration of tolerance under these conditions was less than 60 min. These results demonstrate that tolerance to the discriminative stimulus effects of nicotine can be produced by acute nicotine exposure. Acute cross-tolerance from nicotine to varenicline is consistent with similar actions at nAChRs, and suggests that conditions resulting in acute nicotine tolerance could impact sensitivity to other nAChR agonists.
机译：急性耐受尼古丁的影响在尼古丁依赖中起重要作用，但这些效果的机制尚不清楚。目前研究药物歧视用于研究尼古丁预处理对尼古丁和FDA批准的吸烟药物治疗varenicline的敏感性对鉴别刺激作用的敏感性的影响。恒河猴（n = 4）根据刺激终止的FR5节目在盐水中区分了0.032mg / kg尼古丁基IV。尼古丁和恒生线均增加药物适当的响应; ED50值（95％置信限制）分别为0.0087 [0.0025,0.030]和0.028 [0.0096,0.082] Mg / kg。尼古丁训练剂量（0.032mg / kg，iv）的额外预处理注射耐受其辨别刺激效应的耐受性，并且这种效果的大小与施用的预处理注射的数量有关。尼古丁训练剂量的两种预处理注射（0.032mg / kg，iv）在尼古丁剂量 - 响应函数中产生了5.4倍的右转，并且在横向剂量响应函数中的七倍右移。在这些条件下耐受性的持续时间小于60分钟。这些结果表明，对尼古丁的鉴别刺激作用的耐受性可以通过急性尼古丁暴露产生。来自尼古丁至varenicline的急性交通与NACHRS的相似作用一致，表明导致急性尼古丁耐受性可能会影响对其他NACHR激动剂的敏感性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号