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Psychopharmacology

, Volume 113, Issue 3–4, pp 318–321 | Cite as

Reduction in ATP-sensitive potassium channel-mediated antinociception in diabetic mice

  • Junzo Kamei
  • Naoya Kawashima
  • Minoru Narita
  • Tsutomu Suzuki
  • Miwa Misawa
  • Yutaka Kasuya
Original Investigations

Abstract

To test our hypothesis that the abnormally low efficacy of μ-opioid agonists in diabetic mice may be due to functional changes in ATP-sensitive potassium channels, we evaluated the effects of cromakalim on the tail-flick latencies in diabetic and non-diabetic mice. Anti nociceptive effects of morphine (10 µg, ICV) in diabetic mice were significantly less than that in non-diabetic mice. Morphine-induced antinociception in non-diabetic mice was antagonized by pretreatment with glibenclamide (30 µg, ICV), an ATP-sensitive potassium channel blocker. Cromakalim (0.3 and 1 µg, ICV) produced significant, dose-dependent antinociception in non-diabetic mice, which was significantly reduced by pretreatment with glibenclamide. However, cromakalim did not markedly affect the tail-flick latencies in diabetic mice, even at higher doses (3 µg, ICV). On the other hand, [D-Pen2,5]enkephaline (DPDPE, 5 µg, ICV), a selective δ-opioid receptor agonist, produced significant antinociception in both diabetic and non-diabetic mice. Since pretreatment with glibenclamide significantly reduced the antinociceptive effect of DPDPE in non-diabetic mice but not in diabetic mice, δ-opioid receptor-mediated antinociception in diabetic mice may be independent of potassium channels. These results suggest that dysfunction of ATP-sensitive potassium channels may contribute to the demonstrated poor antinociceptive response of diabetic mice to μ-opioid agonists.

Key words

Diabetes Antinociception Cromakalim Glibenclamide Adenosine triphosphate (ATP)-sensitive potassium channel Morphine [D-Pen2,5]enkephalin 

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Junzo Kamei
    • 1
  • Naoya Kawashima
    • 1
  • Minoru Narita
    • 1
  • Tsutomu Suzuki
    • 1
  • Miwa Misawa
    • 1
  • Yutaka Kasuya
    • 1
  1. 1.Department of Pharmacology, Faculty of Pharmaceutical SciencesHoshi UniversityTokyoJapan

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