在体光药理学与被笼闭的μ阿片受体激动剂共同作用导致行为的快速变化。
In vivo photopharmacology with a caged mu opioid receptor agonist drives rapid changes in behavior.
机构信息
Department of Neurobiology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, L'Hospitalet de Llobregat, Catalonia, Spain.
出版信息
Nat Methods. 2023 May;20(5):682-685. doi: 10.1038/s41592-023-01819-w. Epub 2023 Mar 27.
Abstract
Photoactivatable drugs and peptides can drive quantitative studies into receptor signaling with high spatiotemporal precision, yet few are compatible with behavioral studies in mammals. We developed CNV-Y-DAMGO-a caged derivative of the mu opioid receptor-selective peptide agonist DAMGO. Photoactivation in the mouse ventral tegmental area produced an opioid-dependent increase in locomotion within seconds of illumination. These results demonstrate the power of in vivo photopharmacology for dynamic studies into animal behavior.
摘要
光激活药物和肽可以在高时空精度下驱动受体信号的定量研究，但很少有药物与哺乳动物的行为研究兼容。我们开发了 CNV-Y-DAMGO，一种 µ 阿片受体选择性肽激动剂 DAMGO 的笼状衍生物。在小鼠腹侧被盖区进行光激活，在光照后的几秒钟内产生了阿片类药物依赖性的运动增加。这些结果证明了体内光药理学在动物行为的动态研究中的强大功能。
相似文献
1
In vivo photopharmacology with a caged mu opioid receptor agonist drives rapid changes in behavior.在体光药理学与被笼闭的μ阿片受体激动剂共同作用导致行为的快速变化。
Nat Methods. 2023 May;20(5):682-685. doi: 10.1038/s41592-023-01819-w. Epub 2023 Mar 27.
2
Reciprocal opioid-opioid interactions between the ventral tegmental area and nucleus accumbens regions in mediating mu agonist-induced feeding in rats.腹侧被盖区与伏隔核区域之间的阿片类物质相互作用在介导大鼠μ激动剂诱导的进食中的作用
Peptides. 2005 Apr;26(4):621-9. doi: 10.1016/j.peptides.2004.11.007. Epub 2004 Dec 15.
3
Functional selectivity and time-dependence of μ-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area.小鼠腹侧被盖区神经末梢处μ-阿片受体脱敏的功能选择性和时间依赖性。
Br J Pharmacol. 2015 Jan;172(2):469-81. doi: 10.1111/bph.12605. Epub 2014 Jul 1.
4
The mu opioid agonist DAMGO alters the intravenous self-administration of cocaine in rats: mechanisms in the ventral tegmental area.μ阿片受体激动剂DAMGO改变大鼠静脉注射可卡因的自我给药行为：腹侧被盖区的机制
Psychopharmacology (Berl). 1999 Feb;141(4):428-35. doi: 10.1007/s002130050853.
5
Prolonged effects of repeated social defeat stress on mRNA expression and function of mu-opioid receptors in the ventral tegmental area of rats.重复社会挫败应激对大鼠腹侧被盖区μ-阿片受体mRNA表达及功能的长期影响。
Neuropsychopharmacology. 2005 Jun;30(6):1096-103. doi: 10.1038/sj.npp.1300658.
6
Mu Opioid Receptor Agonist DAMGO Produces Place Conditioning, Abstinence-induced Withdrawal, and Naltrexone-Dependent Locomotor Activation in Planarians.μ 阿片受体激动剂 DAMGO 在水螅中产生位置条件作用、戒断诱导性撤退和纳曲酮依赖性运动激活。
Neuroscience. 2018 Aug 21;386:214-222. doi: 10.1016/j.neuroscience.2018.06.029. Epub 2018 Jun 27.
7
Opioid modulation of ventral pallidal afferents to ventral tegmental area neurons.阿片类物质调制腹侧苍白球传入纤维至腹侧被盖区神经元。
J Neurosci. 2013 Apr 10;33(15):6454-9. doi: 10.1523/JNEUROSCI.0178-13.2013.
8
Alterations in food intake elicited by GABA and opioid agonists and antagonists administered into the ventral tegmental area region of rats.向大鼠腹侧被盖区注射γ-氨基丁酸（GABA）、阿片类激动剂和拮抗剂所引发的食物摄入量变化。
Physiol Behav. 2002 May 1;76(1):107-16. doi: 10.1016/s0031-9384(02)00690-x.
9
Opioid receptor agonists selective for mu and kappa receptors attenuate methamphetamine-induced behavioral sensitization in the mouse.对μ和κ受体具有选择性的阿片受体激动剂可减弱小鼠中甲基苯丙胺诱导的行为敏化。
Biol Pharm Bull. 1996 Mar;19(3):369-74. doi: 10.1248/bpb.19.369.
10
Mu and kappa opioid agonists modulate ventral tegmental area input to the ventral pallidum.μ和κ阿片类激动剂调节腹侧被盖区向腹侧苍白球的输入。
Eur J Neurosci. 2002 Jan;15(2):257-68. doi: 10.1046/j.0953-816x.2001.01860.x.
引用本文的文献
1
Opioid Receptors Modulate Inhibition within the Prefrontal Cortex Through Dissociable Cellular and Molecular Mechanisms.阿片受体通过可分离的细胞和分子机制调节前额叶皮层内的抑制作用。
J Neurosci. 2025 May 20. doi: 10.1523/JNEUROSCI.1963-24.2025.
2
Conceptual expansion of photomedicine for spatiotemporal treatment methods.光医学在时空治疗方法方面的概念拓展。
RSC Med Chem. 2025 Mar 11. doi: 10.1039/d4md01005a.
3
Mu and Delta Opioid Receptors Modulate Inhibition within the Prefrontal Cortex Through Dissociable Cellular and Molecular Mechanisms.μ和δ阿片受体通过可分离的细胞和分子机制调节前额叶皮质内的抑制作用。
bioRxiv. 2024 Oct 21:2024.10.17.618870. doi: 10.1101/2024.10.17.618870.
4
Neuromodulator and neuropeptide sensors and probes for precise circuit interrogation in vivo.用于在体精确检测神经回路的神经调质和神经肽传感器及探针。
Science. 2024 Sep 27;385(6716):eadn6671. doi: 10.1126/science.adn6671.
5
A 'double-edged' role for type-5 metabotropic glutamate receptors in pain disclosed by light-sensitive drugs.光敏感药物揭示了 5 型代谢型谷氨酸受体在疼痛中的“双刃剑”作用。
Elife. 2024 Aug 22;13:e94931. doi: 10.7554/eLife.94931.
6
Multiple layers of diversity govern the cell type specificity of GABAergic input received by mouse subicular pyramidal neurons.多层次的多样性控制着 GABA 能传入小鼠海马锥体细胞的细胞类型特异性。
J Physiol. 2024 Sep;602(17):4195-4213. doi: 10.1113/JP286679. Epub 2024 Aug 14.
7
Unlocking opioid neuropeptide dynamics with genetically encoded biosensors.利用基因编码生物传感器揭示阿片类神经肽动态变化。
Nat Neurosci. 2024 Sep;27(9):1844-1857. doi: 10.1038/s41593-024-01697-1. Epub 2024 Jul 15.
8
Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology.氘代作为增强基于偶氮苯的光药理学的一般策略。
Angew Chem Int Ed Engl. 2024 Sep 23;63(39):e202408300. doi: 10.1002/anie.202408300. Epub 2024 Aug 19.
9
Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.蓝斑核从导水管周围灰质和头端腹内侧髓质接受的输入塑造了阿片介导的下行性疼痛调制。
Sci Adv. 2024 Apr 26;10(17):eadj9581. doi: 10.1126/sciadv.adj9581.
10
Genetically Encoded Photocatalysis Enables Spatially Restricted Optochemical Modulation of Neurons in Live Mice.基因编码光催化实现对活体小鼠神经元的空间受限光化学调控。
ACS Cent Sci. 2023 Dec 18;10(1):163-175. doi: 10.1021/acscentsci.3c01351. eCollection 2024 Jan 24.
本文引用的文献
1
Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons.μ 阿片受体和 δ 阿片受体在海马区钙结合蛋白阳性中间神经元中汇聚、功能独立的信号转导。
Elife. 2021 Nov 17;10:e69746. doi: 10.7554/eLife.69746.
2
An endogenous opioid circuit determines state-dependent reward consumption.内源性阿片样物质回路决定状态依赖型奖赏消费。
Nature. 2021 Oct;598(7882):646-651. doi: 10.1038/s41586-021-04013-0. Epub 2021 Oct 13.
3
Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors.细胞特异性光可切换激动剂，用于可逆控制内源性多巴胺受体。
Nat Commun. 2021 Aug 6;12(1):4775. doi: 10.1038/s41467-021-25003-w.
4
Photopharmacology Enabled by Multifunctional Fibers.多功能纤维实现的光药理学
ACS Chem Neurosci. 2020 Nov 18;11(22):3802-3813. doi: 10.1021/acschemneuro.0c00577. Epub 2020 Oct 27.
5
Relocation of an Extrasynaptic GABA Receptor to Inhibitory Synapses Freezes Excitatory Synaptic Strength and Preserves Memory.将 GABA 受体从突触外转移到抑制性突触会冻结兴奋性突触强度并保留记忆。
Neuron. 2021 Jan 6;109(1):123-134.e4. doi: 10.1016/j.neuron.2020.09.037. Epub 2020 Oct 22.
6
Photocontrol of Endogenous Glycine Receptors In Vivo.体内内源性甘氨酸受体的光控。
Cell Chem Biol. 2020 Nov 19;27(11):1425-1433.e7. doi: 10.1016/j.chembiol.2020.08.005. Epub 2020 Aug 25.
7
Biased signaling by endogenous opioid peptides.内源性阿片肽的偏倚信号转导。
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11820-11828. doi: 10.1073/pnas.2000712117. Epub 2020 May 11.
8
Branched Photoswitchable Tethered Ligands Enable Ultra-efficient Optical Control and Detection of G Protein-Coupled Receptors In Vivo.分支光可切换的连接配体可实现对体内 G 蛋白偶联受体的超高效率光学控制和检测。
Neuron. 2020 Feb 5;105(3):446-463.e13. doi: 10.1016/j.neuron.2019.10.036. Epub 2019 Nov 26.
9
Battery-free, lightweight, injectable microsystem for in vivo wireless pharmacology and optogenetics.用于体内无线药理学和光遗传学的无电池、轻量级、可注射微系统。
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21427-21437. doi: 10.1073/pnas.1909850116. Epub 2019 Oct 10.
10
Optical control of neuronal ion channels and receptors.光控神经元离子通道和受体。
Nat Rev Neurosci. 2019 Sep;20(9):514-532. doi: 10.1038/s41583-019-0197-2.
Zotero 插件