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μ阿片受体阻断对精神兴奋剂诱导的大鼠背侧纹状体中前强啡肽原、c-fos和zif/268信使核糖核酸表达的调节作用

Regulation of psychostimulant-induced preprodynorphin, c-fos and zif/268 messenger RNA expression in the rat dorsal striatum by mu opioid receptor blockade.

作者信息

Horner Kristen A, Keefe Kristen A

机构信息

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.

出版信息

Eur J Pharmacol. 2006 Feb 17;532(1-2):61-73. doi: 10.1016/j.ejphar.2005.12.041. Epub 2006 Jan 27.

Abstract

Several studies have shown that psychostimulants can induce differential immediate early gene and neuropeptide expression in the patch versus matrix compartments of dorsal striatum. The patch compartment contains a high density of mu opioid receptors and activation of these receptors may contribute to psychostimulant-induced gene expression in the patch versus matrix compartments of dorsal striatum. However, the contribution of mu opioid receptor activation to psychostimulant-induced changes in gene expression in the patch compartment of dorsal striatum has not been examined. The current study examined the role of mu opioid receptors in psychostimulant induction of preprodynorphin, c-fos and zif/268 messenger RNA expression in the patch versus matrix compartments of dorsal striatum. Male Sprague-Dawley rats were treated with the mu opioid receptor antagonist, clocinnamox (1 mg/kg, s.c.), 24 h prior to treatment with cocaine (30 mg/kg, i.p.) or methamphetamine (15 mg/kg, s.c.) and sacrificed 45 min or 3 h later. Mu opioid receptor antagonism blocked psychostimulant-induced preprodynorphin messenger RNA expression only in the rostral patch compartment, whereas psychostimulant-induced zif/268 messenger RNA expression in the patch and matrix compartments was attenuated throughout the dorsal striatum. Clocinnamox pretreatment had no effect on stimulant-induced increases in c-fos expression. These data suggest that mu opioid receptor activation plays a specific role in psychostimulant-induced preprodynorphin messenger RNA expression in the rostral patch compartment and zif/268 messenger RNA expression throughout dorsal striatum.

摘要

多项研究表明,精神兴奋剂可在背侧纹状体的斑块与基质区室中诱导不同的即刻早期基因和神经肽表达。斑块区室含有高密度的μ阿片受体,这些受体的激活可能有助于精神兴奋剂在背侧纹状体的斑块与基质区室中诱导基因表达。然而,μ阿片受体激活对精神兴奋剂诱导的背侧纹状体斑块区室基因表达变化的作用尚未得到研究。本研究考察了μ阿片受体在精神兴奋剂诱导背侧纹状体斑块与基质区室中前强啡肽原、c-fos和zif/268信使核糖核酸表达中的作用。雄性Sprague-Dawley大鼠在给予可卡因(30毫克/千克,腹腔注射)或甲基苯丙胺(15毫克/千克,皮下注射)前24小时,皮下注射μ阿片受体拮抗剂氯辛那明(1毫克/千克),并在45分钟或3小时后处死。μ阿片受体拮抗作用仅在吻侧斑块区室阻断了精神兴奋剂诱导的前强啡肽原信使核糖核酸表达,但在整个背侧纹状体中,精神兴奋剂诱导的斑块和基质区室中的zif/268信使核糖核酸表达均减弱。氯辛那明预处理对兴奋剂诱导的c-fos表达增加没有影响。这些数据表明,μ阿片受体激活在精神兴奋剂诱导的吻侧斑块区室前强啡肽原信使核糖核酸表达以及整个背侧纹状体zif/268信使核糖核酸表达中发挥特定作用。

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