• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

短期和长期吗啡暴露后不同脑区磷酸化CREB表达的变化：与食物摄入的关系。

Alterations in phosphorylated CREB expression in different brain regions following short- and long-term morphine exposure: relationship to food intake.

作者信息

Ren Xiuhai, Lutfy Kabirullah, Mangubat Michael, Ferrini Monica G, Lee Martin L, Liu Yanjun, Friedman Theodore C

机构信息

Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Charles R. Drew University of Medicine and Science and UCLA School of Medicine, 1731 E. 120th. Street, Los Angeles, CA 90059, USA.

出版信息

J Obes. 2013;2013:764742. doi: 10.1155/2013/764742. Epub 2013 Aug 29.

DOI:10.1155/2013/764742
PMID:24073333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3773431/
Abstract

BACKGROUND

Activation of the cyclic adenosine monophosphate (cAMP)/phosphorylated CREB (P-CREB) system in different brain regions has been implicated in mediating opioid tolerance and dependence, while alteration of this system in the lateral hypothalamus (LH) has been suggested to have a role in food intake and body weight.

METHODS

Given that opioids regulate food intake, we measured P-CREB in different brain regions in mice exposed to morphine treatments designed to induce different degrees of tolerance and dependence.

RESULTS

We found that a single morphine injection or daily morphine injections for 8 days did not influence P-CREB levels, while the escalating dose of morphine regimen raised P-CREB levels only in the ventral tegmental area (VTA). Chronic morphine pellet implantation for 7 days raised P-CREB levels in the LH, VTA, and dorsomedial nucleus of the hypothalamus (DM) but not in the nucleus accumbens and amygdala. Increased P-CREB levels in LH, VTA, and DM following 7-day treatment with morphine pellets and increased P-CREB levels in the VTA following escalating doses of morphine were associated with decreased food intake and body weight.

CONCLUSION

The morphine regulation of P-CREB may explain some of the physiological sequelae of opioid exposure including altered food intake and body weight.

摘要

背景

不同脑区中环磷酸腺苷（cAMP）/磷酸化环磷腺苷反应元件结合蛋白（P-CREB）系统的激活与阿片类药物耐受性和依赖性的介导有关，而下丘脑外侧区（LH）中该系统的改变被认为在食物摄入和体重方面发挥作用。

方法

鉴于阿片类药物调节食物摄入，我们在接受旨在诱导不同程度耐受性和依赖性的吗啡治疗的小鼠的不同脑区中测量了P-CREB。

结果

我们发现单次注射吗啡或每日注射吗啡8天对P-CREB水平没有影响，而递增剂量的吗啡方案仅使腹侧被盖区（VTA）的P-CREB水平升高。慢性植入吗啡微丸7天可使LH、VTA和下丘脑背内侧核（DM）的P-CREB水平升高，但伏隔核和杏仁核的P-CREB水平未升高。吗啡微丸治疗7天后LH、VTA和DM中P-CREB水平升高以及递增剂量吗啡后VTA中P-CREB水平升高与食物摄入量和体重下降有关。

结论

吗啡对P-CREB的调节可能解释了阿片类药物暴露的一些生理后果，包括食物摄入和体重的改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/f575cf68768d/JOBES2013-764742.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/bf1065995e71/JOBES2013-764742.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/49cda3d58363/JOBES2013-764742.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/8eb93bd38baf/JOBES2013-764742.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/f7108b80773d/JOBES2013-764742.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/f575cf68768d/JOBES2013-764742.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/bf1065995e71/JOBES2013-764742.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/49cda3d58363/JOBES2013-764742.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/8eb93bd38baf/JOBES2013-764742.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/f7108b80773d/JOBES2013-764742.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208b/3773431/f575cf68768d/JOBES2013-764742.005.jpg

相似文献

1
Alterations in phosphorylated CREB expression in different brain regions following short- and long-term morphine exposure: relationship to food intake.短期和长期吗啡暴露后不同脑区磷酸化CREB表达的变化：与食物摄入的关系。
J Obes. 2013;2013:764742. doi: 10.1155/2013/764742. Epub 2013 Aug 29.
2
Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence.激素原转化酶2（PC2）基因敲除小鼠的μ阿片受体水平升高，同时吗啡诱导的镇痛、耐受性和依赖性也发生改变。
Neuroscience. 2016 Aug 4;329:318-25. doi: 10.1016/j.neuroscience.2016.05.021. Epub 2016 May 18.
3
Behavioral and molecular effects of dopamine D1 receptor stimulation during naloxone-precipitated morphine withdrawal.纳洛酮诱发吗啡戒断期间多巴胺D1受体刺激的行为和分子效应
J Neurosci. 2006 Jun 14;26(24):6450-7. doi: 10.1523/JNEUROSCI.0491-06.2006.
4
Chronic morphine administration induces over-expression of aldolase C with reduction of CREB phosphorylation in the mouse hippocampus.长期给予吗啡会诱导小鼠海马体中醛缩酶C的过表达，并伴有CREB磷酸化水平降低。
Eur J Pharmacol. 2009 May 1;609(1-3):51-7. doi: 10.1016/j.ejphar.2009.03.028. Epub 2009 Mar 14.
5
Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats.内侧伏隔核 CB1 受体在蛋白水平上对伏隔核和腹侧被盖区 c-fos 和 pCREB/CREB 比值的调节作用，以及在大鼠的消退和吗啡寻求中的作用。
Brain Res Bull. 2018 Sep;142:320-327. doi: 10.1016/j.brainresbull.2018.08.017. Epub 2018 Aug 28.
6
Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum.在大鼠纹状体原代培养物中，诱发吗啡戒断期间，多巴胺依赖性地增加环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化水平。
J Neurochem. 2003 Oct;87(1):107-18. doi: 10.1046/j.1471-4159.2003.01992.x.
7
Differential regulation of prohormone convertase 1/3, prohormone convertase 2 and phosphorylated cyclic-AMP-response element binding protein by short-term and long-term morphine treatment: implications for understanding the "switch" to opiate addiction.短期和长期吗啡治疗对激素原转化酶1/3、激素原转化酶2及磷酸化环磷酸腺苷反应元件结合蛋白的差异调节：对理解向阿片类药物成瘾“转变”的意义
Neuroscience. 2008 Oct 15;156(3):788-99. doi: 10.1016/j.neuroscience.2008.07.063. Epub 2008 Aug 9.
8
Naloxone-precipitated withdrawal enhances ERK phosphorylation in prefrontal association cortex and accumbens nucleus of morphine-dependent mice.纳洛酮诱发的戒断增强了吗啡依赖小鼠前额叶联合皮层和伏隔核中 ERK 的磷酸化。
Neurosci Lett. 2010 Jan 14;468(3):348-52. doi: 10.1016/j.neulet.2009.11.030. Epub 2009 Nov 14.
9
Inhibition of opioid systems in the hypothalamus as well as the mesolimbic area suppresses feeding behavior of mice.抑制下丘脑以及中脑边缘区域的阿片类系统会抑制小鼠的进食行为。
Neuroscience. 2015 Dec 17;311:9-21. doi: 10.1016/j.neuroscience.2015.10.002. Epub 2015 Oct 24.
10
Glucocorticoid receptor but not mineralocorticoid receptor mediates the activation of ERK pathway and CREB during morphine withdrawal.糖皮质激素受体而非盐皮质激素受体介导吗啡戒断期间细胞外信号调节激酶（ERK）通路和环磷腺苷效应元件结合蛋白（CREB）的激活。
Addict Biol. 2017 Mar;22(2):342-353. doi: 10.1111/adb.12328. Epub 2015 Nov 24.

引用本文的文献

1
Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.μ-阿片受体信号传导的分子和细胞基础：耐受性和依赖性发展的潜在机制。
Front Neurosci. 2025 Jun 24;19:1597922. doi: 10.3389/fnins.2025.1597922. eCollection 2025.
2
Phospho-CREB Regulation on NMDA Glutamate Receptor 2B and Mitochondrial Calcium Uniporter in the Ventrolateral Periaqueductal Gray Controls Chronic Morphine Withdrawal in Male Rats.磷酸化 CREB 对腹外侧导水管周围灰质中 NMDA 谷氨酸受体 2B 和线粒体钙单向转运体的调控作用控制雄性大鼠的慢性吗啡戒断反应
J Neurosci. 2025 Jul 16;45(29):e1934242025. doi: 10.1523/JNEUROSCI.1934-24.2025.
3

本文引用的文献

1
Gene expression profiling following short-term and long-term morphine exposure in mice uncovers genes involved in food intake.短期和长期吗啡暴露后小鼠的基因表达谱分析揭示了参与食物摄入的基因。
Neuroscience. 2010 May 5;167(2):554-66. doi: 10.1016/j.neuroscience.2010.01.043. Epub 2010 Feb 6.
2
Regulation of energy stores and feeding by neuronal and peripheral CREB activity in Drosophila.果蝇中神经元和外周 CREB 活性对能量储存和摄食的调节。
PLoS One. 2009 Dec 30;4(12):e8498. doi: 10.1371/journal.pone.0008498.
3
Differential regulation of prohormone convertase 1/3, prohormone convertase 2 and phosphorylated cyclic-AMP-response element binding protein by short-term and long-term morphine treatment: implications for understanding the "switch" to opiate addiction.
Preconception opioids interact with mouse strain to alter morphine withdrawal in the next generation.
孕前阿片类药物与小鼠品系相互作用，改变下一代吗啡戒断。
Psychopharmacology (Berl). 2024 Jul;241(7):1435-1446. doi: 10.1007/s00213-024-06574-0. Epub 2024 Mar 19.
4
The role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression.神经递质、应激激素和免疫系统在糖尿病、肥胖症和抑郁症之间的正反馈循环中的作用。
Front Endocrinol (Lausanne). 2023 Aug 17;14:1224612. doi: 10.3389/fendo.2023.1224612. eCollection 2023.
5
The Opioid System in Rainbow Trout Telencephalon Is Probably Involved in the Hedonic Regulation of Food Intake.虹鳟鱼端脑的阿片类系统可能参与食物摄入的享乐调节。
Front Physiol. 2022 Mar 1;13:800218. doi: 10.3389/fphys.2022.800218. eCollection 2022.
6
Integration of Nutrient Sensing in Fish Hypothalamus.鱼类下丘脑的营养感知整合
Front Neurosci. 2021 Feb 26;15:653928. doi: 10.3389/fnins.2021.653928. eCollection 2021.
7
Pentylenetetrazol and Morphine Interaction in a State-dependent Memory Model: Role of CREB Signaling.戊四氮与吗啡在状态依赖记忆模型中的相互作用：CREB信号通路的作用
Basic Clin Neurosci. 2020 Jul-Aug;11(4):557-572. doi: 10.32598/bcn.11.4.1482.1. Epub 2020 Jul 1.
8
The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn.线粒体钙单向转运体通过大鼠脊髓背角的 pCREB 和 CPEB1 促进吗啡耐受。
Br J Anaesth. 2019 Aug;123(2):e226-e238. doi: 10.1016/j.bja.2019.05.027. Epub 2019 Jun 26.
9
Sex differences in the expression of morphine withdrawal symptoms and associated activity in the tail of the ventral tegmental area.吗啡戒断症状表达及相关活动在腹侧被盖区尾部的性别差异。
Neurosci Lett. 2019 Jul 13;705:124-130. doi: 10.1016/j.neulet.2019.04.057. Epub 2019 Apr 28.
10
Response of rainbow trout's (Oncorhynchus mykiss) hypothalamus to glucose and oleate assessed through transcription factors BSX, ChREBP, CREB, and FoxO1.通过转录因子 BSX、ChREBP、CREB 和 FoxO1 评估虹鳟鱼（Oncorhynchus mykiss）下丘脑对葡萄糖和油酸的反应。
J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2018 Nov;204(11):893-904. doi: 10.1007/s00359-018-1288-7. Epub 2018 Sep 17.
短期和长期吗啡治疗对激素原转化酶1/3、激素原转化酶2及磷酸化环磷酸腺苷反应元件结合蛋白的差异调节：对理解向阿片类药物成瘾“转变”的意义
Neuroscience. 2008 Oct 15;156(3):788-99. doi: 10.1016/j.neuroscience.2008.07.063. Epub 2008 Aug 9.
4
The role of beta-endorphin in the acute motor stimulatory and rewarding actions of cocaine in mice.β-内啡肽在可卡因对小鼠的急性运动刺激和奖赏作用中的作用。
Psychopharmacology (Berl). 2008 Apr;197(3):443-8. doi: 10.1007/s00213-007-1053-z. Epub 2008 Jan 6.
5
Regulation of morphine reward and feeding by CREB in the lateral hypothalamus.下丘脑外侧区中CREB对吗啡奖赏和进食的调节作用。
Synapse. 2007 Feb;61(2):110-3. doi: 10.1002/syn.20344.
6
Differential involvement of enkephalins in analgesic tolerance, locomotor sensitization, and conditioned place preference induced by morphine.脑啡肽在吗啡诱导的镇痛耐受、运动敏化和条件性位置偏爱中的不同作用。
Behav Neurosci. 2006 Feb;120(1):10-5. doi: 10.1037/0735-7044.120.1.10.
7
Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior.下丘脑泌素在介导应激诱导的可卡因觅求行为复燃中的作用。
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19168-73. doi: 10.1073/pnas.0507480102. Epub 2005 Dec 15.
8
Is there a common molecular pathway for addiction?成瘾是否存在共同的分子途径？
Nat Neurosci. 2005 Nov;8(11):1445-9. doi: 10.1038/nn1578.
9
A role for lateral hypothalamic orexin neurons in reward seeking.外侧下丘脑食欲素神经元在奖赏寻求中的作用。
Nature. 2005 Sep 22;437(7058):556-9. doi: 10.1038/nature04071. Epub 2005 Aug 14.
10
Melanocortinergic modulation of cholecystokinin-induced suppression of feeding through extracellular signal-regulated kinase signaling in rat solitary nucleus.通过细胞外信号调节激酶信号通路，黑皮质素能对大鼠孤束核中胆囊收缩素诱导的摄食抑制进行调节。
Endocrinology. 2005 Sep;146(9):3739-47. doi: 10.1210/en.2005-0562. Epub 2005 Jun 16.