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    Age-Induced Changes in μ-Opioid Receptor Signaling in the Midbrain Periaqueductal Gray of Male and Female Rats

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    Author
    Fullerton, E.F.
    Karom, M.C.
    Streicher, J.M.
    Young, L.J.
    Murphy, A.Z.
    Affiliation
    Department of Pharmacology, College of Medicine, University of Arizona
    Issue Date
    2022
    Keywords
    advanced age
    chronic pain
    m-opioid receptor
    opioid signaling
    pharmacology
    sex differences
    
    Metadata
    Show full item record
    Publisher
    Society for Neuroscience
    Citation
    Fullerton, E. F., Karom, M. C., Streicher, J. M., Young, L. J., & Murphy, A. Z. (2022). Age-Induced Changes in μ-Opioid Receptor Signaling in the Midbrain Periaqueductal Gray of Male and Female Rats. Journal of Neuroscience, 42(32), 6232–6242.
    Journal
    Journal of Neuroscience
    Rights
    Copyright © 2022 the authors.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Opioids have decreased analgesic potency (but not efficacy) in aged rodents compared with adults; however, the neural mechanisms underlying this attenuated response are not yet known. The present study investigated the impact of advanced age and biological sex on opioid signaling in the ventrolateral periaqueductal gray (vlPAG) in the presence of chronic inflammatory pain. Assays measuring μ-opioid receptor (MOR) radioligand binding, GTPγS binding, receptor phosphorylation, cAMP inhibition, and regulator of G-protein signaling (RGS) protein expression were performed on vlPAG tissue from adult (2-3 months) and aged (16-18 months) male and female rats. Persistent inflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA). Adult males exhibited the highest MOR binding potential (BP) and highest G-protein activation (activation efficiency ratio) in comparison to aged males and females (adult and aged). No impact of advanced age or sex on MOR phosphorylation state was observed. DAMGO-induced cAMP inhibition was highest in the vlPAG of adult males compared with aged males and females (adult and aged). vlPAG levels of RGS4 and RGS9-2, critical for terminating Gprotein signaling, were assessed using RNAscope. Adult rats (both males and females) exhibited lower levels of vlPAG RGS4 and RGS9-2 mRNA expression compared with aged males and females. The observed age-related reductions in vlPAG MOR BP, G-protein activation efficiency, and cAMP inhibition, along with the observed age-related increases in RGS4 and RGS9-2 vlPAG expression, provide potential mechanisms whereby the potency of opioids is decreased in the aged population. © 2022 the authors.
    Note
    6 month embargo; published: 10 August 2022
    ISSN
    0270-6474
    PubMed ID
    35790399
    DOI
    10.1523/JNEUROSCI.0355-22.2022
    Version
    Final published version
    ae974a485f413a2113503eed53cd6c53
    10.1523/JNEUROSCI.0355-22.2022
    Scopus Count
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    UA Faculty Publications

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