Effects of naloxone, morphine and κ-opioid receptor agonists on hypoxia/hypoglycemia-induced reduction of 2-deoxyglucose uptake in hippocampal slices from U-50,488H-tolerant rats

Shigenobu Shibata, Keiko Tominaga, Shigenori Watanabe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The aim of the present study was to determine whether U-50,488H and U-62,066E, κ-opioid receptor agonists cause a neuroprotective action against hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake was prevented by cotreatment with naloxone, an opioid receptor antagonist, but potentiated by cotreatment with morphine, a μ-opioid receptor agonist. Chronic administration of U-50,488H resulted in the development of tolerance to the analgesic effect as well as the neuroprotective effect whereas this treatment affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG uptake. Chronic administration of U-50,488H did not modify naloxone-induced attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced exacerbation. These findings suggest that the tolerance to κ-opioid receptors does not affect the μ-opioid receptor-mediated neuroprotective or neurotoxic action.

Original languageEnglish
Pages (from-to)155-158
Number of pages4
JournalNeuroscience Letters
Volume182
Issue number2
DOIs
Publication statusPublished - 1994 Dec 5
Externally publishedYes

Fingerprint

(trans)-Isomer 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide
mu Opioid Receptor
Deoxyglucose
Opioid Receptors
Naloxone
Hypoglycemia
Morphine
Narcotic Antagonists
Neuroprotective Agents
Analgesics
Hypoxia

Keywords

  • 2-Deoxyglucose
  • Brain slice
  • Hypoxia/hypoglycemia
  • Morphine
  • Tolerance
  • κ-Opioid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Effects of naloxone, morphine and κ-opioid receptor agonists on hypoxia/hypoglycemia-induced reduction of 2-deoxyglucose uptake in hippocampal slices from U-50,488H-tolerant rats",
abstract = "The aim of the present study was to determine whether U-50,488H and U-62,066E, κ-opioid receptor agonists cause a neuroprotective action against hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake was prevented by cotreatment with naloxone, an opioid receptor antagonist, but potentiated by cotreatment with morphine, a μ-opioid receptor agonist. Chronic administration of U-50,488H resulted in the development of tolerance to the analgesic effect as well as the neuroprotective effect whereas this treatment affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG uptake. Chronic administration of U-50,488H did not modify naloxone-induced attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced exacerbation. These findings suggest that the tolerance to κ-opioid receptors does not affect the μ-opioid receptor-mediated neuroprotective or neurotoxic action.",
keywords = "2-Deoxyglucose, Brain slice, Hypoxia/hypoglycemia, Morphine, Tolerance, κ-Opioid",
author = "Shigenobu Shibata and Keiko Tominaga and Shigenori Watanabe",
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AU - Tominaga, Keiko

AU - Watanabe, Shigenori

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AB - The aim of the present study was to determine whether U-50,488H and U-62,066E, κ-opioid receptor agonists cause a neuroprotective action against hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake was prevented by cotreatment with naloxone, an opioid receptor antagonist, but potentiated by cotreatment with morphine, a μ-opioid receptor agonist. Chronic administration of U-50,488H resulted in the development of tolerance to the analgesic effect as well as the neuroprotective effect whereas this treatment affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG uptake. Chronic administration of U-50,488H did not modify naloxone-induced attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced exacerbation. These findings suggest that the tolerance to κ-opioid receptors does not affect the μ-opioid receptor-mediated neuroprotective or neurotoxic action.

KW - 2-Deoxyglucose

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