Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats.
Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats.
复制标题
芬地林对斯普拉格-道利大鼠甲基苯丙胺诱导的条件性位置偏好的维持和表达的影响。
DOI：
10.1007/s00213-013-3347-7
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发表时间：
2014
影响因子：
3.4
通讯作者：
Napier,TCeleste
中科院分区：
文献类型：
--
作者：
Voigt,RobinM;Riddle,JenniferL;Napier,TCeleste
RationaleFendiline是一种gabab受体阳性变构调节剂和l型Ca2+通道阻滞剂，可安全用于人类。基于这些药理特性，芬地林可能有助于破坏可能导致吸毒成瘾个体复发的联想记忆。目的：本研究利用条件位置偏好（CPP）在大鼠中评估了芬地林抑制甲基苯丙胺（冰毒）和环境背景之间习得关联的维持和表达的潜力。方法在甲基苯丙胺条件作用（1 mg/kg）后，在不同的条件作用后时间给药芬地兰（5 mg/kg），以确定是否存在芬地兰有效的时间窗口。结果不论后处理时间长短，2次/ d注射非迪兰对CPP维持无影响，10次/ d注射非迪兰对CPP维持有抑制作用（p< 0.05）。在CPP试验之前立即给药的芬地兰抑制了大鼠甲基诱导的CPP的表达，这些大鼠的芬地兰治疗史为每天注射10次（p< 0.05），或在10天治疗的最后2天注射两次（p< 0.05）。芬地宁本身不会产生偏好或厌恶，也不会改变动机运动行为。结论在CPP检测前，反复给药芬地林可减轻甲基苯丙胺CPP的维持和表达。降低冰毒相关线索的重要性可以减少复发；因此，对于戒断的冰毒成瘾者来说，芬地兰可能是一种有价值的成瘾疗法。
RationaleFendiline is a GABABreceptor-positive allosteric modulator and L-type Ca2+channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individualsObjectiveThe current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humansMethodsFollowing meth conditioning (1 mg/kg), fendiline (5 mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective.ResultsTwo once-daily injections of fendiline did not influence themaintenanceof CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPPmaintenance(p< 0.05). Fendiline administered immediately prior to the CPP test inhibitedexpressionof meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p< 0.05) or those that received two injections that corresponded to the last 2 days of the 10-day treatment (p< 0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior.ConclusionMaintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans.