Lobelane decreases methamphetamine self-administration in rats
Lobelane decreases methamphetamine self-administration in rats
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DOI：
10.1016/j.ejphar.2007.06.003
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发表时间：
2007-10-01
影响因子：
5
通讯作者：
Bardo, Michael T.
中科院分区：
文献类型：
--
作者：
Neugebauer, Nichole M.;Harrod, Steven B.;Bardo, Michael T.
半边莲碱是一种半边莲的次要生物碱，也是一种合成的半边莲碱的脱氧类似物，对囊泡单胺转运蛋白和多巴胺转运蛋白具有良好的亲和力。目前的研究审查了。洛贝拉烷特异性减少甲基苯丙胺自我给药的能力。以固定比率5强化时间表训练大鼠以自我施用甲基苯丙胺（0.05mg/kg/输注，i. v.）或对蔗糖颗粒有反应。在达到稳定反应后，大鼠用洛贝烷（0. 1、1、3、5.6或10 mg/kg，s.c.）或生理盐水，手术前15分钟。为了评估重复洛贝烷对甲基苯丙胺自我给药的影响，将大鼠用洛贝烷（5.6或10 mg/kg，s.c.）7个会议。行为特异性通过评估洛贝兰（0. 1、1、3、5或10 mg/kg，s.c.）或生理盐水对自发活动的影响在测试的剂量范围内，洛贝兰剂量依赖性地减少甲基苯丙胺自我管理，而没有影响蔗糖维持反应。仅在给予最高剂量的洛贝烷（10 mg/ kg）后，自发活动降低。在重复的预处理中，对洛贝兰对甲基苯丙胺自我给药的作用产生了耐受性，表明洛贝兰特异性降低甲基苯丙胺自我给药的能力是一种短暂的作用。因此，综合考虑，结果表明，尽管洛贝林与被认为是其减少甲基苯丙胺自我给药能力的原因的药理学靶标相互作用，但从洛贝林分子中除去氧官能团可能提供了具有改变的药代动力学和/或药效学特征的化合物。(c)2007 Elsevier B. V.保留所有权利。
Lobelane, a minor alkaloid of Lobelia inflata and a synthetic, des-oxy analog of lobeline, has good affinity for the vesicular monoamine transporter and the dopamine transporter. The current study examined the. ability of lobelane to specifically decrease methamphetamine self-administration. Rats were trained on a fixed ratio 5 schedule of reinforcement to self-administer methamphetamine (0.05 mg/kg/infusion, i.v.) or to respond for sucrose pellets. Upon reaching stable responding, rats were pretreated with lobelane (0. 1, 1, 3, 5.6, or 10 mg/kg, s.c.) or saline, 15 min prior to the operant session. To assess the effect of repeated lobelane on methamphetamine self-administration, rats were pretreated with lobelane (5.6 or 10 mg/kg, s.c.) for 7 sessions. Behavioral specificity was further investigated by assessing the effects of lobelane (0. 1, 1, 3, 5, or 10 mg/kg, s.c.) or saline on locomotor activity. Within the dose range tested, lobelane dose-dependently decreased methamphetamine self-administration, while having no effect on sucrose-maintained responding. Locomotor activity was decreased following only the highest dose of lobelane (10 mg/ kg). Across repeated pretreatments, tolerance developed to the effect of lobelane on methamphetamine self-administration, demonstrating that the ability of lobelane to specifically decrease methamphetamine self-administration is a transient effect. Thus, taken together, the results show that although lobelane interacts with the pharmacological targets believed to be responsible for its ability to decrease metbamphetamine self-administration, removal of the oxygen functionalities from the lobeline molecule may have afforded a compound with an altered pharmacokinetic and/or pharmacodynamic profile. (c) 2007 Elsevier B.V. All rights reserved.