Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats
Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats
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DOI：
10.1016/j.ejphar.2008.11.031
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发表时间：
2009-01-14
影响因子：
5
通讯作者：
Gong, Ze-Hui
中科院分区：
文献类型：
--
作者：
Liu, Yan-Li;Yan, Ling-Di;Gong, Ze-Hui
左旋四氢延胡索乙素（l-THP）是从中药延胡索和千金藤中纯化得到的生物碱，存在于许多传统中药制剂中。我们之前的研究证明了 I-THIP 能够抑制小鼠和大鼠由羟考酮引起的运动刺激和身体依赖性。本研究旨在使用条件位置偏好测定评估 l-THP 对羟考酮奖励的影响。羟考酮（0.32-5.0 mg/kg）诱导大鼠条件性位置偏爱的发展。此外，羟考酮（2.5 mg/kg）诱导伏隔核和海马中 CREB 和 ERK 的磷酸化增加，但在前额皮质中则不然。 l-THP（6.25-18.50 mg/kg）本身不能诱导条件性位置偏好或条件性位置厌恶。在调节过程中，l-THP 与羟考酮共同给药部分消除了羟考酮诱导的大鼠条件性位置偏爱的发展。此外，l-THP 抑制大鼠伏核和海马中 ERK 和 CREB 磷酸化的增加。这些结果表明，l-THP可以通过影响大鼠伏核和海马CREB和ERK的磷酸化来抑制羟考酮引起的心理依赖。目前的数据与之前的发现相结合，支持 I-THIP 治疗羟考酮成瘾的潜在用途。 (C) 2008 Elsevier B.V. 保留所有权利。
Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from the Chinese herb corydalis and stephania and is contained in many traditional Chinese herbal preparations. Our previous studies demonstrated the ability of I-THIP to inhibit locomotor stimulation and physical dependence induced by oxycodone in mice and rats. The present study was designed to evaluate effects of l-THP on reward of oxycodone using conditioned place preference assay. Oxycodone (0.32-5.0 mg/kg) induced the development of conditioned place preference in rats. Furthermore, oxycodone (2.5 mg/kg) induced the increased phosphorylation of CREB and ERK in nucleus accumbens and hippocampus, but not in prefrontal cortex. l-THP (6.25-18.50 mg/kg) per se was not able to induce conditioned place preference or conditioned place aversion. l-THP co-administered with oxycodone during the conditioning sessions partly abolished the development of oxycodone-induced conditioned place preference in rats. Furthermore, l-THP inhibited the increased phosphorylation of ERK and CREB in nucleus accumbens and hippocampus of rats. All these results suggest that l-THP can inhibit oxycodone-induced psychological dependence by affecting phosphorylation of CREB and ERK in nucleus accumbens and hippocampus of rats. Together, the present data, combined with previous finding, support the potential use of I-THIP for treatment of oxycodone addiction. (C) 2008 Elsevier B.V. All rights reserved.