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消旋γ-乙烯基-GABA(R,S-GVG)可阻断甲基苯丙胺引发的条件性位置偏好恢复。

Racemic gamma vinyl-GABA (R,S-GVG) blocks methamphetamine-triggered reinstatement of conditioned place preference.

作者信息

DeMarco Amy, Dalal Reema M, Pai Jessica, Aquilina Stefanie D, Mullapudi Uma, Hammel Crystie, Kothari Shiva K, Kahanda Milan, Liebling Courtney N B, Patel Vinal, Schiffer Wynne K, Brodie Jonathan D, Dewey Stephen L

机构信息

Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.

出版信息

Synapse. 2009 Feb;63(2):87-94. doi: 10.1002/syn.20582.

Abstract

Preventing relapse poses a significant challenge to the successful management of methamphetamine (METH) dependence. Although no effective medication currently exists for its treatment, racemic gamma vinyl-GABA (R,S-GVG, vigabatrin) shows enormous potential as it blocks both the neurochemical and behavioral effects of a variety of drugs, including METH, heroin, morphine, ethanol, nicotine, and cocaine. Using the reinstatement of a conditioned place preference (CPP) as an animal model of relapse, the present study specifically investigated the ability of an acute dose of R,S-GVG to block METH-triggered reinstatement of a METH-induced CPP. Animals acquired a METH CPP following a 20-day-period of conditioning, in which they received 10 pairings of alternating METH and saline injections. During conditioning, rats were assigned to one of four METH dosage groups: 1.0, 2.5, 5.0, or 10.0 mg/kg (i.p., n = 8/group). Animals in all dosage groups demonstrated a robust and consistent CPP. This CPP was subsequently extinguished in each dosage group with repeated saline administration. Upon extinction, all groups reinstated following an acute METH challenge. On the following day, an acute dose of R,S-GVG (300 mg/kg, i.p.) was administered 2.5 h prior to an identical METH challenge. R,S-GVG blocked METH-triggered reinstatement in all four groups. Given that drug re-exposure may potentiate relapse to drug-seeking behavior, the ability of R,S-GVG to block METH-triggered reinstatement offers further support for its use in the successful management of METH dependence.

摘要

预防复发对成功治疗甲基苯丙胺(METH)依赖构成了重大挑战。尽管目前尚无有效的药物治疗方法,但消旋γ-乙烯基-GABA(R,S-GVG,氨己烯酸)显示出巨大潜力,因为它能阻断包括METH、海洛因、吗啡、乙醇、尼古丁和可卡因在内的多种药物的神经化学和行为效应。本研究以条件性位置偏爱(CPP)恢复作为复发的动物模型,专门研究了急性剂量的R,S-GVG阻断METH引发的METH诱导的CPP恢复的能力。动物在经过20天的条件训练后获得了METH CPP,在此期间它们接受了10次METH和生理盐水交替注射。在条件训练期间,大鼠被分配到四个METH剂量组之一:1.0、2.5、5.0或10.0 mg/kg(腹腔注射,每组n = 8)。所有剂量组的动物都表现出强烈且一致的CPP。随后,通过重复注射生理盐水,每个剂量组的这种CPP都被消除。消退后,所有组在急性METH激发后都出现了恢复。在接下来的一天,在相同的METH激发前2.5小时给予急性剂量的R,S-GVG(腹腔注射300 mg/kg)。R,S-GVG在所有四个组中都阻断了METH引发的恢复。鉴于药物再次接触可能会增强对觅药行为的复发,R,S-GVG阻断METH引发的恢复的能力为其在成功治疗METH依赖中的应用提供了进一步支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b8c/5004629/e0fd42d26014/nihms66355f1.jpg

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