Acute cocaine increases phosphorylation of CaMKII and GluA1 in the dorsolateral striatum of drug naïve rats, but not cocaine-experienced rats.
Acute cocaine increases phosphorylation of CaMKII and GluA1 in the dorsolateral striatum of drug naïve rats, but not cocaine-experienced rats.
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DOI：
10.1016/j.neulet.2013.01.017
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发表时间：
2013-03-14
影响因子：
2.5
通讯作者：
Pierce RC
中科院分区：
文献类型：
--
作者：
White SL;Schmidt HD;Vassoler FM;Pierce RC
含有GluA1的AMPA谷氨酸受体向伏核中突触的运输，这一过程涉及CaMKII对关键丝氨酸残基的磷酸化，与可卡因寻找行为的恢复有关。越来越多的证据表明，背侧纹状体与可卡因成瘾有关。然而，在可卡因恢复期间，CaMKII介导的背外侧纹状体GluA1亚单位的磷酸化的潜在作用还没有被研究。在这项研究中，大鼠接受了自我注射可卡因的训练，并与接受生理盐水注射的盐水挂钩的大鼠配对。灭绝后，每对大鼠分别接受系统注射可卡因(10 mg/kg，ip)。或者生理盐水。正如预期的那样，可卡因经验的大鼠对挑战注射的反应显示出强劲的可卡因寻求恢复，而带轭的生理盐水对照组则没有。在恢复测试后立即解剖双侧纹状体。Western blotting实验结果显示，急性注射可卡因后，盐水成瘾大鼠双侧纹状体内pGluA1-ser831和pCaMKII-thr286表达增加。在接受生理盐水注射的可卡因经历的大鼠中没有这种影响，在可卡因经历的大鼠中预先注射可卡因后也没有观察到任何变化。这些结果表明，在药物幼稚大鼠中，急性暴露于可卡因增加了CaMKII介导的含GluA1的纹状体内AMPA受体的磷酸化，这一效应在可卡因激发诱导的药物寻找恢复过程中没有观察到。因此，急性可卡因后CaMKII和GluA1的磷酸化增加是DL纹状体的一种代偿机制，这是可能的。
Transport of GluA1-containing AMPA glutamate receptors to synapses in the nucleus accumbens, a process that involves phosphorylation of key serine residues by CaMKII, is associated with the reinstatement of cocaine-seeking behavior. A growing body of evidence indicates that the dorsal striatum contributes to aspects of cocaine addiction. However, the potential role of CaMKII-mediated phosphorylation of GluA1 subunits in the dorsolateral (DL) striatum during cocaine reinstatement has not been examined. In this study, rats were trained to self-administer cocaine and were partnered with saline-yoked rats that received injections of saline. Following extinction, each pair of rats received either a systemic priming injection of cocaine (10 mg/kg, i.p.) or saline. As expected, cocaine-experienced rats displayed robust reinstatement of cocaine seeking in response to a challenge injection, whereas yoked saline controls did not. The DL striatum was dissected immediately following the reinstatement test session. Results from Western blotting experiments showed increased pGluA1-ser831 and pCaMKII-thr286 in the DL striatum of saline-yoked rats given an acute injection of cocaine. This effect was absent in cocaine-experienced rats that received a saline injection, and no changes were observed following a priming injection of cocaine in cocaine-experienced rats. These results indicate that acute exposure to cocaine in drug naïve rats increased CaMKII-mediated phosphorylation of GluA1-containing AMPA receptors in the DL striatum, an effect that was not observed during cocaine priming-induced reinstatement of drug seeking. It is possible; therefore, that increased phosphorylation of CaMKII and GluA1 following acute cocaine is a compensatory mechanism in the DL striatum.
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影响因子：
5.3
作者：
Vanderschuren, LJMJ;Di Ciano, P;Everitt, BJ
通讯作者：
Everitt, BJ
DOI：
10.1016/j.bbrc.2008.12.003
发表时间：
2009-01-30
影响因子：
3.1
作者：
Kim, Myonghwan;Au, Eunkyu;Yoon, Bong-June
通讯作者：
Yoon, Bong-June
影响因子：
3.3
作者：
Mckee, NL;Meshul, CK
通讯作者：
Meshul, CK
DOI：
10.1111/j.1749-6632.2009.05144.x
发表时间：
2010-01-01
期刊：
ADDICTION REVIEWS 2
影响因子：
--
作者：
Schmidt, Heath D.;Pierce, R. Christopher
通讯作者：
Pierce, R. Christopher
DOI：
10.1038/npp.2012.104
发表时间：
2012-10
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
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