Reversal of morphine antinociceptive tolerance by acute spinal inhibition of Ca2+/calmodulin-dependent protein kinase II

It has been reported that Ca2+/calmodulin-dependent protein kinase 11 (CaMKII) can modulate opioid tolerance via its action on learning and memory. In this study, we examine if CaMKII can directly affect opioid tolerance. We found that spinal CaMKII activity was increased in rats tolerant to morphine. In these rats, acute spinal administration of 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) (KN93), a CaMKII inhibitor, was able to reverse the already-established antinociceptive tolerance. These results suggest that CaMKII may directly promote opioid tolerance. (C) 2003 Elsevier Science B.V. All rights reserved.