Alcohol-induced sedation and synergistic interactions between alcohol and morphine: A key mechanistic role for Toll-like receptors and MyD88-dependent signaling

Highlights • Drug–drug interactions such as alcohol–morphine represent a significant clinical burden. • TLR2–MyD88–NF-κB signaling is critical to this synergistic drug–drug interaction. • Central nervous system innate immunology may be a novel site of unwanted drug-drug interactions....

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Published in:Brain, behavior, and immunity behavior, and immunity, 2015-03, Vol.45, p.245-252
Main Authors: Corrigan, Frances, Wu, Yue, Tuke, Jonathan, Coller, Janet K, Rice, Kenner C, Diener, Kerrilyn R, Hayball, John D, Watkins, Linda R, Somogyi, Andrew A, Hutchinson, Mark R
Format: Article
Language:English
Subjects:
Allergy and Immunology
Analgesics, Opioid - pharmacology
Animals
Central Nervous System - drug effects
Central Nervous System Depressants - pharmacology
Cytokines
Drug interactions
Drug overdose
Drug Synergism
Ethanol - pharmacology
Interleukin-1beta - drug effects
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Morphine - pharmacology
Myeloid differentiation factor 88
Myeloid Differentiation Factor 88 - drug effects
Myeloid Differentiation Factor 88 - genetics
Naloxone
NF-kappa B - drug effects
Psychiatry
Receptors, Opioid, mu - drug effects
Reflex, Abnormal
Signal Transduction
Toll like receptors
Toll-Like Receptor 2 - drug effects
Toll-Like Receptor 2 - genetics
Toll-Like Receptor 4 - drug effects
Toll-Like Receptor 4 - genetics
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Summary:Highlights • Drug–drug interactions such as alcohol–morphine represent a significant clinical burden. • TLR2–MyD88–NF-κB signaling is critical to this synergistic drug–drug interaction. • Central nervous system innate immunology may be a novel site of unwanted drug-drug interactions.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2014.12.019