Group I metabotropic glutamate receptor-mediated activation of PKC gamma in the nucleus accumbens core promotes the reinstatement of cocaine seeking.
Group I metabotropic glutamate receptor-mediated activation of PKC gamma in the nucleus accumbens core promotes the reinstatement of cocaine seeking.
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DOI：
10.1111/adb.12122
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发表时间：
2015-03
影响因子：
3.4
通讯作者：
Pierce RC
中科院分区：
文献类型：
--
作者：
Schmidt HD;Kimmey BA;Arreola AC;Pierce RC
越来越多的证据表明，伏核中的I型代谢型谷氨酸受体(MGluRs)在可卡因寻找过程中起着关键作用。本研究试图确定伏隔核mGluR1mGluR5和蛋白激酶C(PKC)在可卡因诱导的药物再寻找中的作用。在这里，我们表明伏隔内核心给予mGluR1/5激动剂DHPG(250μM)促进了大鼠的可卡因寻找。与这些结果一致的是，在预先注射可卡因(10 mg/kg)之前，将mGluR1(50μMym 298198)或mGluR5(9.0μM mpep)拮抗剂直接注入伏隔核可减弱寻求药物的恢复。MGluR1/5刺激激活包括PKC在内的一系列信号转导通路。核内微量注射PKC抑制剂(10μM RO31-82 2 0或30.0μM白屈菜红碱)也可钝化对可卡因的寻求。此外，可卡因诱导的药物寻找的恢复与核心区PKCγ的磷酸化增加有关，而与PKCα或PKCβII的磷酸化无关。药物抑制伏隔核心区mGluR1、mGluR5或PKC对蔗糖寻觅无影响。综上所述，这些发现表明，伏隔核中的mGluR1和mGluR5激活促进了可卡因的寻找，并且这些影响是增强剂特有的。此外，刺激伏隔核内的mGluR1和mGluR5可能部分通过激活蛋白激酶Cγ来调节可卡因寻找。
Emerging evidence indicates that type I metabotropic glutamate receptors (mGluRs) in the nucleus accumbens play a critical role in cocaine seeking. The present study sought to determine the role of accumbens core mGluR1, mGluR5 and protein kinase C (PKC) in cocaine priming-induced reinstatement of drug seeking. Here, we show that intra-accumbens core administration of the mGluR1/5 agonist DHPG (250 μM) promoted cocaine seeking in rats. Consistent with these results, administration of an mGluR1 (50.0 μM YM 298198) or mGluR5 (9.0 μM MPEP) antagonist directly into the accumbens core prior to a priming injection of cocaine (10 mg/kg) attenuated the reinstatement of drug seeking. mGluR1/5 stimulation activates a signaling cascade including PKC. Intracore microinjection of PKC inhibitors (10 μM Ro 31–8220 or 30.0 μM chelerythrine) also blunted cocaine seeking. In addition, cocaine priming-induced reinstatement of drug seeking was associated with increased phosphorylation of PKCγ, but not PKCα or PKCβII, in the core. There were no effects of pharmacological inhibition of mGluR1, mGluR5 or PKC in the accumbens core on sucrose seeking. Together, these findings indicate that mGluR1 and mGluR5 activation in the accumbens core promotes cocaine seeking and that these effects are reinforcer specific. Furthermore, stimulation of mGluR1 and mGluR5 in the accumbens core may regulate cocaine seeking, in part, through activation of PKCγ.
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影响因子：
5.2
作者：
Lee AM;Messing RO
通讯作者：
Messing RO
DOI：
10.1523/jneurosci.5884-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li YQ;Xue YX;He YY;Li FQ;Xue LF;Xu CM;Sacktor TC;Shaham Y;Lu L
通讯作者：
Lu L
影响因子：
3.3
作者：
Narita, M;Akai, H;Suzuki, T
通讯作者：
Suzuki, T
DOI：
10.1523/jneurosci.3625-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
McCutcheon JE;Loweth JA;Ford KA;Marinelli M;Wolf ME;Tseng KY
通讯作者：
Tseng KY
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