First Author | Ko SW | Year | 2006 |
Journal | Eur J Neurosci | Volume | 23 |
Issue | 8 | Pages | 2158-68 |
PubMed ID | 16630062 | Mgi Jnum | J:108062 |
Mgi Id | MGI:3622954 | Doi | 10.1111/j.1460-9568.2006.04748.x |
Citation | Ko SW, et al. (2006) Evidence for a role of CaMKIV in the development of opioid analgesic tolerance. Eur J Neurosci 23(8):2158-68 |
abstractText | 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. |