دورية أكاديمية
أعرض في EDS

Oxycodone-Mediated Activation of the Mu Opioid Receptor Reduces Whole Brain Functional Connectivity in Mice.

التفاصيل البيبلوغرافية
العنوان: Oxycodone-Mediated Activation of the Mu Opioid Receptor Reduces Whole Brain Functional Connectivity in Mice.
المؤلفون: Nasseef MT; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., Singh JP; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., Ehrlich AT; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., McNicholas M; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., Park DW; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., Ma W; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., Kulkarni P; Center for Translational Neuro-Imaging, Northeastern University, Boston, Massachusetts 02115, United States., Kieffer BL; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada., Darcq E; Douglas Hospital Research Center, Department of Psychiatry, School of Medicine, McGill University, Montreal, Quebec H4H 1R3, Canada.
المصدر: ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2019 Jun 28; Vol. 2 (4), pp. 264-274. Date of Electronic Publication: 2019 Jun 28 (Print Publication: 2019).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101721411 Publication Model: eCollection Cited Medium: Internet ISSN: 2575-9108 (Electronic) Linking ISSN: 25759108 NLM ISO Abbreviation: ACS Pharmacol Transl Sci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Chemical Society, [2018]-
مستخلص: Oxycodone is a potent medicinal opioid analgesic to treat pain. It is also addictive and a main cause for the current opioid crisis. At present, the impact of oxycodone on coordinated brain network activities, and contribution of the mu opioid receptor (MOR) to these effects, is unknown. We used pharmacological magnetic resonance imaging in mice to characterize MOR-mediated oxycodone effects on whole-brain functional connectivity (FC). Control (CTL) and MOR knockout (KO) animals were imaged under dexmedetomidine in a 7Tesla scanner. Acquisition was performed continuously before and after 2 mg/kg oxycodone administration (analgesic in CTL mice). Independent component analysis (data-driven) produced a correlation matrix, showing widespread oxycodone-induced reduction of FC across 71 components. Isocortex, nucleus accumbens (NAc), pontine reticular nucleus, and periacqueducal gray (PAG) components showed the highest number of significant changes. Seed-to-voxel FC analysis (hypothesis-driven) was then focused on PAG and NAc considered key pain and reward centers. The two seeds showed reduced FC with 8 and 22 Allen Brain Atlas-based regions, respectively, in CTL but not KO mice. Further seed-to-seed quantification showed highest FC modifications of both PAG and NAc seeds with hypothalamic and amygdalar areas, as well as between them, revealing the strongest impact across reward and aversion/pain centers of the brain. In conclusion, we demonstrate that oxycodone reduces brain communication in a MOR-dependent manner, and establish a preliminary whole-brain FC signature of oxycodone. This proof-of-principle study provides a unique platform and reference data set to test other MOR opioid agonists and perhaps discover new mechanisms and FC biomarkers predicting safer analgesics.
Competing Interests: The authors declare no competing financial interest.
(Copyright © 2019 American Chemical Society.)
References: Exp Neurol. 2012 Apr;234(2):382-8. (PMID: 22245158)
Anesth Analg. 1993 Feb;76(2):266-73. (PMID: 8424502)
Pharmacol Rev. 2013 Jan 15;65(1):223-54. (PMID: 23321159)
Annu Rev Public Health. 2015 Mar 18;36:559-74. (PMID: 25581144)
J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56. (PMID: 15907646)
Curr Opin Pharmacol. 2013 Oct;13(5):813-20. (PMID: 23856429)
Psychopharmacology (Berl). 2010 Oct;212(2):193-203. (PMID: 20665209)
Trends Pharmacol Sci. 2013 Apr;34(4):206-14. (PMID: 23465410)
J Pharmacol Exp Ther. 2013 Apr;345(1):41-51. (PMID: 23370795)
Commun Biol. 2018 Aug 6;1:102. (PMID: 30271982)
Nat Rev Neurosci. 2011 Oct 05;12(11):685-700. (PMID: 21971065)
Neuroimage. 2004 Jul;22(3):1214-22. (PMID: 15219593)
Biol Psychiatry. 2017 May 1;81(9):778-788. (PMID: 28185645)
Trends Neurosci. 2015 Nov;38(11):741-750. (PMID: 26603560)
Psychopharmacology (Berl). 2016 May;233(10):1991-2004. (PMID: 26344108)
Br J Pharmacol. 2015 Apr;172(8):2148-64. (PMID: 25521524)
Behav Pharmacol. 2013 Sep;24(5-6):504-16. (PMID: 23839029)
Neuroimage. 2014 Aug 1;96:203-15. (PMID: 24718287)
Neuroimage. 2007 Feb 1;34(3):1042-53. (PMID: 17169578)
Annu Rev Neurosci. 2016 Jul 8;39:297-324. (PMID: 27145915)
BMJ Support Palliat Care. 2018 Jun;8(2):117-128. (PMID: 29331953)
Nature. 2015 Aug 20;524(7565):315-21. (PMID: 26245379)
Trends Neurosci. 2015 Apr;38(4):217-25. (PMID: 25637939)
Cell. 2009 Oct 16;139(2):267-84. (PMID: 19837031)
Neuroscience. 2019 Feb 1;398:88-101. (PMID: 30550747)
Nat Rev Neurosci. 2018 Aug;19(8):499-514. (PMID: 29934561)
J Neurosci Methods. 2012 Feb 15;204(1):9-18. (PMID: 22068031)
J Pain Res. 2018 Feb 08;11:301-311. (PMID: 29445297)
Neuropsychopharmacology. 2012 Apr;37(5):1288-96. (PMID: 22218090)
Stat Methods Med Res. 2003 Oct;12(5):419-46. (PMID: 14599004)
Expert Opin Ther Targets. 2019 Apr;23(4):315-326. (PMID: 30802415)
Curr Opin Pharmacol. 2017 Feb;32:77-84. (PMID: 27936408)
Hum Brain Mapp. 2013 Oct;34(10):2635-54. (PMID: 22611030)
Biol Psychiatry. 2018 Aug 1;84(3):202-212. (PMID: 29580570)
J Psychopharmacol. 2014 Dec;28(12):1115-24. (PMID: 25237122)
Front Pharmacol. 2015 Oct 21;6:231. (PMID: 26539115)
Bull World Health Organ. 2017 May 1;95(5):318-319. (PMID: 28479631)
Physiol Rev. 2009 Oct;89(4):1379-412. (PMID: 19789384)
J Pain Symptom Manage. 1993 Feb;8(2):63-7. (PMID: 8492004)
Nature. 1996 Oct 31;383(6603):819-23. (PMID: 8893006)
Sci Rep. 2019 Mar 11;9(1):4044. (PMID: 30858487)
Prog Brain Res. 1988;77:31-46. (PMID: 3064173)
Expert Opin Drug Discov. 2011 Jun 1;6(6):597-617. (PMID: 21765857)
Brain Struct Funct. 2015 Mar;220(2):677-702. (PMID: 24623156)
Neuropsychopharmacology. 2019 Jan;44(2):259-273. (PMID: 30283002)
Lancet Psychiatry. 2016 Aug;3(8):760-773. (PMID: 27475769)
Psychopharmacology (Berl). 2005 Aug;180(4):761-73. (PMID: 15778889)
Pain Physician. 2017 Feb;20(2S):SE33-SE52. (PMID: 28226340)
Brain Connect. 2017 Oct;7(8):526-540. (PMID: 28882062)
Front Neurosci. 2016 Nov 03;10:471. (PMID: 27857679)
Psychoneuroendocrinology. 2017 Jul;81:52-62. (PMID: 28412582)
J Opioid Manag. 2018 Jan/Feb;14(1):52-60. (PMID: 29508896)
معلومات مُعتمدة: P50 DA005010 United States DA NIDA NIH HHS
تواريخ الأحداث: Date Created: 20200408 Latest Revision: 20200928
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7088903
DOI: 10.1021/acsptsci.9b00021
PMID: 32259060
قاعدة البيانات: MEDLINE
الوصف
تدمد:2575-9108
DOI:10.1021/acsptsci.9b00021