Implications of protein kinase C in the nucleus accumbens in the development of sensitization to methamphetamine in rats
Implications of protein kinase C in the nucleus accumbens in the development of sensitization to methamphetamine in rats
复制标题
DOI：
10.1016/j.neuroscience.2004.06.017
复制
发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Narita, M;Akai, H;Suzuki, T
重复使用甲基苯丙胺导致甲基苯丙胺诱导的多巴胺释放及其相关行为的增强。这种现象称为致敏或逆转耐受。蛋白激酶C（PKC）通过其磷酸化包括其它激酶的靶蛋白的能力控制许多信号级联。本研究的目的是探讨PKC在甲基苯丙胺诱导的奖赏效应和细胞外多巴胺释放增敏中的作用。本研究采用条件性位置偏爱实验和在体微透析技术。一种选择性PKC抑制剂chelerythrine氯化物的核内注射取消甲基苯丙胺诱导的位置偏爱的增强甲基苯丙胺重复治疗后的多巴胺。此外，内注射chelerythrine氯化物阻断多巴胺释放的敏感性的发展，并减少主要的多巴胺代谢产物，3'4-二羟基苯乙酸和高香草酸，在重复甲基苯丙胺治疗诱导的神经核。在这些条件下，胞浆磷酸化的常规或经典型PKC在边缘前脑区，包括核的免疫反应性略有增加，但在甲基苯丙胺致敏大鼠显着。目前的数据提供了证据的暗示PKC在丘脑核中的发展致敏甲基苯丙胺诱导的奖励效应，多巴胺释放和抑制多巴胺代谢/再摄取的大鼠。(C)2004年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Repeated treatment with methamphetamine leads to an enhancement in the methamphetamine-induced dopamine release and its related behaviors. This phenomenon is called sensitization or reverse tolerance. Protein kinase C (PKC) controls numerous signaling cascades by virtue of its ability to phosphorylate target proteins that include other kinases. The purpose of study was then to investigate the implication of PKC in the development of sensitization to the rewarding effect and to the extracellular dopamine release induced by methamphetamine in rats. The conditioned place preference paradigm and in vivo microdialysis assay were performed in the present study. An intra-nucleus accumbens injection of a selective PKC inhibitor chelerythrine chloride abolished the enhancement of the methamphetamine-induced place preference following repeated treatment with methamphetamine. Furthermore, intra-nucleus accumbens injection of chelerythrine chloride blocked the development of sensitization to dopamine release and to the decrease in the major dopamine metabolites, 3'4-dihydroxyphenylacetic acid and homovanillic acid, in the nucleus accumbens induced by repeated methamphetamine treatment. Under these conditions, the immunoreactivity of the cytosolic phosphorylated conventional- or classic-type PKC in the limbic forebrain region including the nucleus accumbens was slightly, but significantly increased in methamphetamine-sensitized rats. The present data provide evidence for the implication of PKC in the nucleus accumbens in the development of sensitization to the methamphetamine-induced rewarding effect, dopamine release and inhibition of dopamine metabolism/reuptake in rats. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.