کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7281353 | 1473922 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Alcohol-induced sedation and synergistic interactions between alcohol and morphine: A key mechanistic role for Toll-like receptors and MyD88-dependent signaling
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
NF-κBMORMYD88LORRIL-1RATLRNMDAN-methyl-d-aspartateμ Opioid receptor - μ گیرنده اپیوئیدinterleukin-1 receptor antagonist - آنتاگونیست گیرنده اینترلوکین-1Loss of righting reflex - از دست دادن رفلکس درست کردنgamma-aminobutyric acid - اسید گاما آمینو بوتیریکDrug interactions - تداخل داروییToll-like receptor - تیالآرCNS - دستگاه عصبی مرکزیCytokines - سیتوکین هاcentral nervous system - سیستم عصبی مرکزیmyeloid differentiation factor 88 - عامل تمایز میلوئید 88nuclear factor-κB - فاکتور هسته ای κBToll like receptors - مانند گیرنده هاdrug overdose - مصرف بیش از حد مواد مخدرNaloxone - نالوکسانmyeloid differentiation primary response gene 88 - پاسخ اولیه ژن 88، اختلال میلوئیدGABA - گابا
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Increasing evidence demonstrates induction of proinflammatory Toll-like receptor (TLR) 2 and TLR4 signaling by morphine and, TLR4 signaling by alcohol; thus indicating a common site of drug action and a potential novel innate immune-dependent hypothesis for opioid and alcohol drug interactions. Hence, the current study aimed to assess the role of TLR2, TLR4, MyD88 (as a critical TLR-signaling participant), NF-κB, Interleukin-1β (IL-1β; as a downstream proinflammatory effector molecule) and the μ opioid receptor (MOR; as a classical site for morphine action) in acute alcohol-induced sedation (4.5 g/kg) and alcohol (2.5 g/kg) interaction with morphine (5 mg/kg) by assessing the loss of righting reflex (LORR) as a measure of sedation. Wild-type male Balb/c mice and matched genetically-deficient TLR2, TLR4, and MyD88 strains were utilized, together with pharmacological manipulation of MOR, NF-κB, TLR4 and Interleukin-1β. Alcohol induced significant LORR in wild-type mice; this was halved by MyD88 and TLR4 deficiency, and surprisingly nearly completely eliminated by TLR2 deficiency. In contrast, the interaction between morphine and alcohol was found to be MOR-, NF-κB-, TLR2- and MyD88-dependent, but did not involve TLR4 or Interleukin-1β. Morphine-alcohol interactions caused acute elevations in microglial cell counts and NF-κB-p65 positive cells in the motor cortex in concordance with wild-type and TLR2 deficient mouse behavioral data, implicating neuroimmunopharmacological signaling as a pivotal mechanism in this clinically problematic drug-drug interaction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 45, March 2015, Pages 245-252
Journal: Brain, Behavior, and Immunity - Volume 45, March 2015, Pages 245-252
نویسندگان
Frances Corrigan, Yue Wu, Jonathan Tuke, Janet K. Coller, Kenner C. Rice, Kerrilyn R. Diener, John D. Hayball, Linda R. Watkins, Andrew A. Somogyi, Mark R. Hutchinson,