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Type: Journal article
Title: Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia
Author: Hutchinson, M.
Northcutt, A.
Chao, L.
Kearney, J.
Zhang, Y.
Berkelhammer, D.
Loram, L.
Rozeske, R.
Bland, S.
Gleeson, T.
Watkins, L.
Maier, S.
Citation: Brain, Behavior, and Immunity, 2008; 22(8):1248-1256
Publisher: Academic Press Inc
Issue Date: 2008
ISSN: 0889-1591
Statement of
Mark R. Hutchinson, Alexis L. Northcutt, Lindsey W. Chao, Jeffrey J. Kearney, Yingning Zhang, Debra L. Berkelhammer, Lisa C. Loram, Robert R. Rozeske, Sondra T. Bland, Steven F. Maier, Todd T. Gleeson and Linda R. Watkins
Abstract: Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here, we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force, and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation.
Keywords: Microglia
Cells, Cultured
Cell Line
Rats, Sprague-Dawley
Respiratory Insufficiency
RNA, Messenger
Pain Measurement
Analysis of Variance
Reverse Transcriptase Polymerase Chain Reaction
Spatial Behavior
Conditioning, Operant
Dose-Response Relationship, Drug
Drug Interactions
Cyclooxygenase 1
Description: Copyright © 2008 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2008.07.008
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Appears in Collections:Aurora harvest
Pharmacology publications

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