Cocaine withdrawal-induced trafficking of delta-opioid receptors in rat nucleus accumbens
Cocaine withdrawal-induced trafficking of delta-opioid receptors in rat nucleus accumbens
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DOI：
10.1016/j.brainres.2008.02.105
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发表时间：
2008-05-19
期刊：
影响因子：
2.9
通讯作者：
Van Bockstaele, Elisabeth J.
中科院分区：
文献类型：
--
作者：
Ambrose-Lanci, Lisa M.;Peiris, Niluk B.;Van Bockstaele, Elisabeth J.
伏核(NAcb)阿片能系统和多巴胺能系统之间的相互作用在介导可卡因戒断对细胞信号和行为的影响中起着关键作用。为了支持这一点，纹状体多巴胺-D1受体(D1R)的激活增加导致在可卡因戒断早期通过腺苷环化酶对增量阿片受体(DOR)信号的脱敏。受体脱敏的潜在细胞底物是受体内化。本研究用免疫电子显微镜观察了可卡因戒断对DOR在NAcb核心(NAcbC)和外壳(NAcbS)树突中的亚细胞定位的影响。雌雄大鼠连续14d灌胃暴饮式可卡因或生理盐水，随后48h戒断。动物经心脏灌流，并对组织切片进行免疫金银定位。半定量分析显示，与生理盐水对照组相比，可卡因戒断导致雌雄大鼠NAcbS和NAcbC细胞内DOR的分布百分比增加。相反，在雌性大鼠的NAcbC中，可卡因戒断后与质膜相关的DOR增加。为了确定D1R的调制是否直接影响含DOR的神经元，在幼年大鼠中验证了DOR和D1R共存于NAcb共同神经元的假说。半定量分析揭示了包含DOR和D1R免疫反应性的图谱的子集。本研究结果证实了可卡因戒断后DOR在NAcb神经元中的重新分布，并为D1R调节NAcb神经元的DOR功能提供了解剖学证据。(C)2008爱思唯尔B.V.保留所有权利。
Interactions between the opioidergic and dopaminergic systems in the nucleus accumbens (NAcb) play a critical role in mediating cocaine withdrawal-induced effects on cell signaling and behavior. In support of this, increased activation of striatal dopamine-D1 receptors (D1R) results in desensitization of delta-opioid receptor (DOR) signaling through adenylyl cyclase during early cocaine withdrawal. A potential cellular substrate underlying receptor desensitization is receptor internalization. The present study examined the effect of cocaine withdrawal on subcellular localization of DOR in dendrites of the NAcb core (NAcbC) and shell (NAcbS) using immunoelectron microscopy. Female and male rats received binge-pattern cocaine or saline for 14 days and subsequently underwent 48 h withdrawal. Animals were transcardially perfused and tissue sections were processed for immunogold-silver localization of DOR. Semi-quantitative analysis revealed that cocaine withdrawal caused an increase in the percentage of DOR localized intracellularly in the NAcbS of male and female rats and the NAcbC of male rats compared to saline controls. In contrast, in the NAcbC of female rats, there was an increase in DOR associated with the plasma membrane following cocaine withdrawal. To determine whether modulation of D1R could directly impact DOR containing neurons, the hypothesis that DOR and D1R co-exist in common neurons of the NAcb was examined in naive rats. Semi-quantitative analysis revealed a subset of profiles containing both DOR and D1R immunoreactivities. The present findings demonstrate a redistribution of DOR in the NAcb following cocaine withdrawal and provide anatomical evidence supporting D1R regulation of DOR function in a subset of NAcb neurons. (C) 2008 Elsevier B.V. All rights reserved.