Evidence for a role of CaMKIV in the development of opioid analgesic tolerance

Shanelle W. Ko, Yongheng Jia, Hui Xu, Se Jeong Yim, Dong Hyuk Jang, Yong Seok Lee, Ming Gao Zhao, Hiroki Toyoda, Long Jun Wu, Talal Chatila, Bong Kiun Kaang, Min Zhuo

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18 Scopus citations

Abstract

cAMP response-element binding protein (CREB), a transcription factor involved in learning, memory and drug addiction, is phosphorylated by calcium-calmodulin-dependent protein kinase IV (CaMKIV). Here, we show that CaMKIV-knockout (KO) mice developed less analgesic tolerance after chronic morphine administration with no alteration in physical dependence or acute morphine-induced analgesia. The increase in phosphorylated CREB expression observed in wild-type mice after chronic morphine was absent in CaMKIV-KO mice, while there was no difference in the expression or phosphorylation of the μ-opioidq2 receptor between groups. Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the μ-opioid receptor than did wild-type mice, while uncoupling was similar in control wild-type and KO mice. In addition, morphine reduced inhibitory transmission to a greater degree in CaMKIV-KO mice than in controlsq3 after chronic morphine exposure. Our results provide novel evidence for the role of CaMKIV in the development of opioid analgesic tolerance but not physical dependence.

Original languageEnglish (US)
Pages (from-to)2158-2168
Number of pages11
JournalEuropean Journal of Neuroscience
Volume23
Issue number8
DOIs
StatePublished - Apr 1 2006

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Keywords

  • CREB
  • Mice
  • Morphine
  • Spinal cord
  • μ-Opioid receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ko, S. W., Jia, Y., Xu, H., Yim, S. J., Jang, D. H., Lee, Y. S., Zhao, M. G., Toyoda, H., Wu, L. J., Chatila, T., Kaang, B. K., & Zhuo, M. (2006). Evidence for a role of CaMKIV in the development of opioid analgesic tolerance. European Journal of Neuroscience, 23(8), 2158-2168. https://doi.org/10.1111/j.1460-9568.2006.04748.x