Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats.
Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats.
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DOI：
10.1016/j.drugalcdep.2010.11.023
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发表时间：
2011-07-01
影响因子：
4.2
通讯作者：
Mantsch, John R.
中科院分区：
文献类型：
--
作者：
Figueroa-Guzman, Yazmin;Mueller, Christopher;Vranjkovic, Oliver;Wisniewski, Samantha;Yang, Zheng;Li, Shi-Jiang;Bohr, Colin;Graf, Evan N.;Baker, David A.;Mantsch, John R.
可卡因成瘾的特点是对药物复吸的敏感性持续增加。因此，确定药物，防止药物复发是药物滥用研究的一个关键目标。药物再暴露、应激性生活事件的发生以及暴露于先前与药物使用相关的线索已被确定为人类复发的决定因素，并已发现恢复大鼠中熄灭的可卡因寻求。本研究检测了急性口服（灌胃）给予左旋四氢巴马汀（l-THP）对可卡因激发后消失的可卡因寻求恢复的影响，左旋四氢巴马汀是一种四氢原小檗碱异喹啉，具有包括拮抗D1、D2和D3多巴胺受体的药理学特征（10 mg/kg，ip）、应激源（不可控电足电击[EFS]）或对先前与雄性Sprague-Dawley大鼠中药物递送相关的刺激（音调和光复合体）的反应依赖性暴露。在iv可卡因自我给药消退后，通过ip可卡因、EFS或溶剂预处理大鼠中药物相关线索的反应相关呈现恢复消退的药物寻求。在恢复试验前1小时口服3.0或10.0 mg/kg L-THP可显著减弱每种刺激的恢复。在10.0 mg/kg的l-THP剂量下，食物强化反应和基线消退后反应显著减弱，但在3.0 mg/kg的l-THP剂量下则没有，这表明3 mg/kg的l-THP对恢复的影响可能与非特异性运动损伤无关。这些发现进一步表明，l-THP可能具有治疗可卡因成瘾的效用。
Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10 mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0 mg/kg l-THP one hour prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0 mg/kg, l-THP dose, indicating that the effects of 3 mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction.
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影响因子：
7.6
作者：
Di Ciano, P;Underwood, RJ;Everitt, BJ
通讯作者：
Everitt, BJ
影响因子：
3.4
作者：
Capriles, N;Rodaros, D;Stewart, J
通讯作者：
Stewart, J
影响因子：
3.4
作者：
Erb, S;Shaham, Y;Stewart, J
通讯作者：
Stewart, J
DOI：
10.1073/pnas.98.4.1976
发表时间：
2001-02-13
影响因子：
11.1
作者：
Ciccocioppo, R;Sanna, PP;Weiss, F
通讯作者：
Weiss, F
影响因子：
2.3
作者：
Gilbert, JG;Newman, AH;Xi, ZX
通讯作者：
Xi, ZX