Role of the calcium/calmodulin-dependent protein kinase ii (CaMKII) in the morphine-induced pharmacological effects in the mouse.
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a family of multifunctional protein kinases that activates signaling pathways. The present study was designed to ascertain whether CaMKII could play a substantial role in the expression of morphine-induced antinociception, hyperlocomotion and rewarding effect in the mouse. An i.c.v. pretreatment with a CaMKII inhibitor KN-93 failed to affect the antinociception and hyperlocomotion induced by s.c. administration of a prototype micro-opioid receptor agonist morphine. In contrast, the morphine-induced place preference was significantly attenuated by i.c.v. pretreatment with KN-93. The levels of phosphorylated-CaMKII (p-CaMKII) in the limbic forebrain, but not in the frontal cortex and the lower midbrain, were significantly increased in morphine-conditioned mice, whereas the levels of CaMKII in three brain regions obtained from morphine-conditioned mice were not changed. This up-regulation of p-CaMKII in the limbic forebrain obtained from morphine-conditioned mice was significantly inhibited by i.c.v. pretreatment with KN-93. These results provide evidence that the increase in CaMKII activity in the mouse limbic forebrain may contribute to the rewarding effect, but not the antinociception and the hyperlocomotion, induced by morphine.
Narita
M
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. narita@hoshi.ac.jp
Matsumura
Y
Y
Ozaki
S
S
Ise
Y
Y
Yajima
Y
Y
Suzuki
T
T
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009020:Morphine; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides