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  • Title: Evidence for a role of CaMKIV in the development of opioid analgesic tolerance.
    Author: Ko SW, Jia Y, Xu H, Yim SJ, Jang DH, Lee YS, Zhao MG, Toyoda H, Wu LJ, Chatila T, Kaang BK, Zhuo M.
    Journal: Eur J Neurosci; 2006 Apr; 23(8):2158-68. PubMed ID: 16630062.
    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 micro-opioid receptor between groups. Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the micro-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 controls 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.
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