Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator.
Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator.
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DOI：
10.1007/s00213-012-2804-z
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发表时间：
2013-01
影响因子：
3.4
通讯作者：
Olive, M. Foster
中科院分区：
文献类型：
--
作者：
Watterson, Lucas R.;Kufahl, Peter R.;Nemirovsky, Natali E.;Sewalia, Kaveish;Hood, Lauren E.;Olive, M. Foster
甲基苯丙胺（METH）是一种强效和成瘾性精神兴奋剂，对使用者的健康有严重的有害影响。目前，METH成瘾通过认知和行为疗法相结合来治疗，但这些传统方法复发率很高。此外，目前没有FDA批准的专门用于治疗METH成瘾的药物治疗干预。代谢型谷氨酸受体5（mGluR5）负变构调节剂（NAM）已显示出在显著减弱药物自我给药和药物寻求恢复范例的前景。然而，缺乏评估已在人类受试者中测试的mGluR5 NAM的潜在功效的研究。目前的研究试图评估mGluR5 NAM非诺班对寻求冰毒行为的影响。训练大鼠自我施用METH（0.05mg/kg静脉内），并且在消退后，测试非诺班（5、10或15 mg/kg i.p.）提示和药物诱导的寻求甲基苯丙胺的恢复。为了确定非诺班是否也改变寻找天然甜味剂的恢复，训练单独的大鼠组自我施用蔗糖或食物颗粒，并测试非诺班对线索诱导的蔗糖和食物寻找的恢复的影响。在10和15 mg/kg剂量下，非诺班减弱了药物和线索诱导的寻找甲基苯丙胺行为的恢复。非诺班还减弱了在所有测试剂量下线索诱导的蔗糖和食物寻求的恢复。mGluR5 NAM fenobam减弱了寻求METH行为的恢复，但这些作用可能是由于对一般食欲行为的非特异性抑制。
Methamphetamine (METH) is a highly potent and addictive psychostimulant with severe detrimental effects to the health of users. Currently, METH addiction is treated with a combination of cognitive and behavioral therapies, but these traditional approaches suffer from high relapse rates. Furthermore, there are currently no pharmacological treatment interventions approved by the FDA specifically for the treatment of METH addiction. Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) have shown promise in significantly attenuating drug self-administration and drug-seeking in reinstatement paradigms. However, studies assessing the potential efficacy of mGluR5 NAMs that have been tested in human subjects are lacking. The current study sought to assess the effect of the mGluR5 NAM fenobam on METH-seeking behavior. Rats were trained to self-administer METH (0.05 mg/kg i.v.), and following extinction, tested for effects of fenobam (5, 10 or 15 mg/kg i.p.) on cue- and drug-induced reinstatement of METH-seeking. To determine if fenobam also alters reinstatement of seeking of natural reinforcers, separate groups of rats were trained to self-administer sucrose or food pellets and were tested for the effects of fenobam on cue-induced reinstatement of sucrose- and food-seeking. Fenobam attenuated drug- and cue-induced reinstatement of METH-seeking behavior at doses of 10 and 15 mg/kg. Fenobam also attenuated cue-induced reinstatement of sucrose- and food-seeking at all doses tested. The mGluR5 NAM fenobam attenuates the reinstatement of METH-seeking behavior, but these effects may be due to non-specific suppression of general appetitive behaviors.
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影响因子：
3.6
作者：
Duncan, Jhodie R.;Lawrence, Andrew J.
通讯作者：
Lawrence, Andrew J.
影响因子：
2.7
作者：
Jaeschke, Georg;Porter, Richard;Spooren, Will
通讯作者：
Spooren, Will
DOI：
10.1124/jpet.103.052027
发表时间：
2003-09-01
影响因子：
3.5
作者：
Kenny, PJ;Gasparini, F;Markou, A
通讯作者：
Markou, A
影响因子：
5.3
作者：
Di Ciano, P;Cardinal, RN;Everitt, BJ
通讯作者：
Everitt, BJ
影响因子：
5.3
作者：
Cornish, JL;Kalivas, PW
通讯作者：
Kalivas, PW