Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 23, Issue 8, Pages 2158-2168Publisher
WILEY
DOI: 10.1111/j.1460-9568.2006.04748.x
Keywords
CREB; mice; morphine; mu-opioid receptor; spinal cord
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Funding
- PHS HHS [42722] Funding Source: Medline
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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 mu-opioid receptor between groups. Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the mu-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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