Activation of mGluR7s inhibits cocaine-induced reinstatement of drug-seeking behavior by a nucleus accumbens glutamate-mGluR2/3 mechanism in rats.
Activation of mGluR7s inhibits cocaine-induced reinstatement of drug-seeking behavior by a nucleus accumbens glutamate-mGluR2/3 mechanism in rats.
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DOI：
10.1111/j.1471-4159.2010.06851.x
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发表时间：
2010-09-01
影响因子：
4.7
通讯作者：
Xi ZX
中科院分区：
文献类型：
--
作者：
Li X;Li J;Gardner EL;Xi ZX
据报道，代谢型谷氨酸受体7（mGluR 7）参与可卡因和酒精自我给药。然而，mGluR 7在药物寻求复发中的作用尚不清楚。使用大鼠复发模型，我们发现全身给予AMN 082，一种选择性mGluR 7变构激动剂，剂量依赖性地抑制可卡因诱导的觅药行为的恢复。将AMN 082颅内微量注射到脑桥核（NAc）或腹侧苍白球（VP）中，但不注射到背侧纹状体（DS）中，也可抑制可卡因引发的恢复，这种作用可通过局部共同施用MMPIP（一种选择性mGluR 7拮抗剂）来阻断。在体内微透析表明，可卡因引发显着增加细胞外多巴胺（DA）的NAc，VP和DS，而增加细胞外谷氨酸的NAc。AMN 082单独未能改变细胞外DA，但仅在NAc中产生细胞外谷氨酸的缓慢发作的持久增加。AMN 082预处理剂量依赖性地阻断可卡因增强的NAc谷氨酸和可卡因诱导的恢复，这种作用被MMPIP或LY 341497（一种选择性mGluR 2/3拮抗剂）阻断。这些数据表明，mGluR 7激活抑制可卡因诱导的药物寻求行为的恢复谷氨酸mGluR 2/3机制在NAc。本研究结果支持mGluR 7激动剂用于治疗可卡因成瘾的潜在用途。
The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown. Using a rat relapse model, we found that systemic administration of AMN082, a selective mGluR7 allosteric agonist, dose-dependently inhibits cocaine-induced reinstatement of drug-seeking behavior. Intracranial microinjections of AMN082 into the nucleus accumbens (NAc) or ventral pallidum (VP), but not the dorsal striatum (DS), also inhibited cocaine-primed reinstatement, an effect that was blocked by local co-administration of MMPIP, a selective mGluR7 antagonist. In vivo microdialysis demonstrated that cocaine priming significantly increased extracellular dopamine (DA) in the NAc, VP and DS, while increasing extracellular glutamate in the NAc only. AMN082 alone failed to alter extracellular DA, but produced a slow-onset long-lasting increase in extracellular glutamate in the NAc only. Pretreatment with AMN082 dose-dependently blocked both cocaine-enhanced NAc glutamate and cocaine-induced reinstatement, an effect that was blocked by MMPIP or LY341497 (a selective mGluR2/3 antagonist). These data suggest that mGluR7 activation inhibits cocaine-induced reinstatement of drug-seeking behavior by a glutamate-mGluR2/3 mechanism in the NAc. The present findings support the potential use of mGluR7 agonists for the treatment of cocaine addiction.
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影响因子：
3.3
作者：
Bari, AA;Pierce, RC
通讯作者：
Pierce, RC
影响因子：
5.3
作者：
Baptista, MAS;Martin-Fardon, R;Weiss, F
通讯作者：
Weiss, F
DOI：
10.1124/jpet.104.078733
发表时间：
2005-03-01
影响因子：
3.5
作者：
Lee, B;Platt, DM;Spealman, RD
通讯作者：
Spealman, RD
影响因子：
5.3
作者：
Cornish, JL;Kalivas, PW
通讯作者：
Kalivas, PW
影响因子：
5.3
作者：
Liechti, Matthias E.;Lhuillier, Loic;Markou, Athina
通讯作者：
Markou, Athina