Astroglial Knockout of Glucocorticoid Receptor Attenuates Morphine Withdrawal Symptoms, but Not Antinociception and Tolerance in Mice.


Journal

Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709

Informations de publication

Date de publication:
Oct 2022
Historique:
received: 23 12 2020
accepted: 24 03 2021
pubmed: 7 4 2021
medline: 31 8 2022
entrez: 6 4 2021
Statut: ppublish

Résumé

The development of tolerance and drug dependence limit the clinical application of opioids for the treatment of severe pain. Glucocorticoid receptors (GRs) are among molecular substrates involved in these processes. Most studies focus on the role of neuronal GR, while the involvement of GR on glial cells is not fully understood. To address this issue, we used a transgenic model of conditional GR knockout mice, targeted to connexin 30-expressing astrocytes, treated with repeated doses of morphine. We observed no difference between control mice and astrocytic GR knockouts in the development of antinociceptive tolerance. Nevertheless, when animals were subjected to precipitated withdrawal, knockouts presented some attenuated symptoms, including jumping. Taken together, our data suggest that hippocampal and spinal astrocytic GRs appear to be involved in opioid withdrawal, and drugs targeting the GR may relieve some symptoms of morphine withdrawal without influencing its antinociceptive properties.

Identifiants

pubmed: 33821329
doi: 10.1007/s10571-021-01086-3
pii: 10.1007/s10571-021-01086-3
pmc: PMC9418269
doi:

Substances chimiques

Analgesics, Opioid 0
Receptors, Glucocorticoid 0
Morphine 76I7G6D29C

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2423-2426

Subventions

Organisme : Narodowe Centrum Nauki
ID : 2013/08/A/NZ3/00848

Informations de copyright

© 2021. The Author(s).

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Auteurs

Magdalena Tertil (M)

Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.

Urszula Skupio (U)

Department of Molecular Neuropharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, ul. Smetna 12, 31-343, Krakow, Poland.

Lucja Kudla (L)

Department of Molecular Neuropharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, ul. Smetna 12, 31-343, Krakow, Poland.

Lucja Wiktorowska (L)

Department of Molecular Neuropharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, ul. Smetna 12, 31-343, Krakow, Poland.

Ryszard Przewlocki (R)

Department of Molecular Neuropharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, ul. Smetna 12, 31-343, Krakow, Poland. nfprzewl@cyf-kr.edu.pl.

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