Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome

Wen Wei Liao, Shih-Ying Tsai, Chia Chi Liao, Kuen Bao Chen, Geng Chang Yeh, Jui Yuan Chen, Yeong-Ray Wen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Glycogen-synthase kinase 3 (GSK3) is involved in many signaling pathways and is associated with a host of high-profile pathophysiological states. However, its role in morphine tolerance, especially naloxone-precipitated withdrawal syndrome, has not been well investigated. The present study was undertaken to study the role of GSK3 in chronic morphine exposure. Methods: Adult male Sprague-Dawley rats were subjected to intraperitoneal (i.p.) injections of morphine (10mg/kg) twice daily for 6 consecutive days, and tail-flick tests were conducted to evaluate changes of morphine-induced antinociception. GSK3 inhibitor, SB216763 or SB415286, was i.p. injected prior to morphine to investigate the influences on morphine tolerance. There were four groups receiving morphine plus vehicle (2% dimethyl sulfoxide), morphine plus SB216763 (0.6mg/kg) or SB415286 (1.0mg/kg), GSK3 inhibitor alone, or dimethyl sulfoxide: as the control group. On Day 7, naloxone (i.p., 1mg/kg) was administered and naloxone-precipitated withdrawal behaviors were individually compared between groups. Results: Repeated morphine exposure in this study led to progressive shortening of tail-flick latencies and produced six of nine observed naloxone-precipitated withdrawal behaviors. Coadministration with SB216763 or SB415286 significantly prevented antinociceptive tolerance and alleviated parts of withdrawal syndrome. Both inhibitors could similarly reverse withdrawal behaviors including grooming, chewing, and ptosis, but did not affect withdrawal behaviors of penis licking and defecation. Conclusion: The results demonstrate the importance of GSK3 in reducing chronic morphine-induced tolerance and withdrawal syndrome. Although GSK3 is involved in diverse physiological functions, aiming at GSK3-related pathway could still be a potential tool to improve therapeutic quality in clinical morphine treatment.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalJournal of the Chinese Medical Association
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Glycogen Synthase Kinase 3
Morphine
Analgesics
Naloxone
Dimethyl Sulfoxide
Tail
Grooming
Defecation
Mastication
Penis
Intraperitoneal Injections
Sprague Dawley Rats

Keywords

  • Glycogen synthase kinase
  • Morphine tolerance
  • Naloxone
  • Withdrawal

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome. / Liao, Wen Wei; Tsai, Shih-Ying; Liao, Chia Chi; Chen, Kuen Bao; Yeh, Geng Chang; Chen, Jui Yuan; Wen, Yeong-Ray.

In: Journal of the Chinese Medical Association, Vol. 77, No. 1, 01.2014, p. 31-37.

Research output: Contribution to journalArticle

Liao, Wen Wei ; Tsai, Shih-Ying ; Liao, Chia Chi ; Chen, Kuen Bao ; Yeh, Geng Chang ; Chen, Jui Yuan ; Wen, Yeong-Ray. / Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome. In: Journal of the Chinese Medical Association. 2014 ; Vol. 77, No. 1. pp. 31-37.
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abstract = "Background: Glycogen-synthase kinase 3 (GSK3) is involved in many signaling pathways and is associated with a host of high-profile pathophysiological states. However, its role in morphine tolerance, especially naloxone-precipitated withdrawal syndrome, has not been well investigated. The present study was undertaken to study the role of GSK3 in chronic morphine exposure. Methods: Adult male Sprague-Dawley rats were subjected to intraperitoneal (i.p.) injections of morphine (10mg/kg) twice daily for 6 consecutive days, and tail-flick tests were conducted to evaluate changes of morphine-induced antinociception. GSK3 inhibitor, SB216763 or SB415286, was i.p. injected prior to morphine to investigate the influences on morphine tolerance. There were four groups receiving morphine plus vehicle (2{\%} dimethyl sulfoxide), morphine plus SB216763 (0.6mg/kg) or SB415286 (1.0mg/kg), GSK3 inhibitor alone, or dimethyl sulfoxide: as the control group. On Day 7, naloxone (i.p., 1mg/kg) was administered and naloxone-precipitated withdrawal behaviors were individually compared between groups. Results: Repeated morphine exposure in this study led to progressive shortening of tail-flick latencies and produced six of nine observed naloxone-precipitated withdrawal behaviors. Coadministration with SB216763 or SB415286 significantly prevented antinociceptive tolerance and alleviated parts of withdrawal syndrome. Both inhibitors could similarly reverse withdrawal behaviors including grooming, chewing, and ptosis, but did not affect withdrawal behaviors of penis licking and defecation. Conclusion: The results demonstrate the importance of GSK3 in reducing chronic morphine-induced tolerance and withdrawal syndrome. Although GSK3 is involved in diverse physiological functions, aiming at GSK3-related pathway could still be a potential tool to improve therapeutic quality in clinical morphine treatment.",
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T1 - Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome

AU - Liao, Wen Wei

AU - Tsai, Shih-Ying

AU - Liao, Chia Chi

AU - Chen, Kuen Bao

AU - Yeh, Geng Chang

AU - Chen, Jui Yuan

AU - Wen, Yeong-Ray

PY - 2014/1

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AB - Background: Glycogen-synthase kinase 3 (GSK3) is involved in many signaling pathways and is associated with a host of high-profile pathophysiological states. However, its role in morphine tolerance, especially naloxone-precipitated withdrawal syndrome, has not been well investigated. The present study was undertaken to study the role of GSK3 in chronic morphine exposure. Methods: Adult male Sprague-Dawley rats were subjected to intraperitoneal (i.p.) injections of morphine (10mg/kg) twice daily for 6 consecutive days, and tail-flick tests were conducted to evaluate changes of morphine-induced antinociception. GSK3 inhibitor, SB216763 or SB415286, was i.p. injected prior to morphine to investigate the influences on morphine tolerance. There were four groups receiving morphine plus vehicle (2% dimethyl sulfoxide), morphine plus SB216763 (0.6mg/kg) or SB415286 (1.0mg/kg), GSK3 inhibitor alone, or dimethyl sulfoxide: as the control group. On Day 7, naloxone (i.p., 1mg/kg) was administered and naloxone-precipitated withdrawal behaviors were individually compared between groups. Results: Repeated morphine exposure in this study led to progressive shortening of tail-flick latencies and produced six of nine observed naloxone-precipitated withdrawal behaviors. Coadministration with SB216763 or SB415286 significantly prevented antinociceptive tolerance and alleviated parts of withdrawal syndrome. Both inhibitors could similarly reverse withdrawal behaviors including grooming, chewing, and ptosis, but did not affect withdrawal behaviors of penis licking and defecation. Conclusion: The results demonstrate the importance of GSK3 in reducing chronic morphine-induced tolerance and withdrawal syndrome. Although GSK3 is involved in diverse physiological functions, aiming at GSK3-related pathway could still be a potential tool to improve therapeutic quality in clinical morphine treatment.

KW - Glycogen synthase kinase

KW - Morphine tolerance

KW - Naloxone

KW - Withdrawal

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