Inhibition of the amygdala and hippocampal calcium/calmodulin-dependent protein kinase II attenuates the dependence and relapse to morphine differently in rats.
Learning and memory have been suggested to play an important role in the development of opiate addiction. Based on the recent finding that calcium/calmodulin protein kinase II (CaMKII) is essential in learning and memory processes, the present study was performed to examine whether inhibition of hippocampal and amygdala CaMKII prevents the dependence and relapse to morphine. The results showed that inhibition of CaMKII by microinjection of specific inhibitors KN-62 into hippocampus decreased the morphine withdrawal syndromes induced by opiate antagonist naloxone. In contrast, inhibition of CaMKII in amygdala failed to do so. Microinjection of KN-62 into both hippocampus and amygdala suppressed the development of formation and reactivation of morphine conditioned place preference (CPP). However, inhibition of CaMKII in amygdala, but not in hippocampus, could attenuate the maintenance of morphine CPP. These results suggest that hippocampal CaMKII is critically involved in the development of morphine physical and psychological dependence, and amygdala CaMKII is some different from hippocampal CaMKII in regulating the dependence and relapse to opiates. Inhibition of this kinase may have some therapeutic benefit in the treatment of opiate dependence and relapse.
Lu
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L
Medical Experimental Center, West China University of Medical Sciences, Chendu, People's Republic of China. lulingg@btamail.net.cn
Zeng
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S
Liu
D
D
Ceng
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X
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D003213:Conditioning, Psychological / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy / Q000201:enzymology*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000201:enzymology
D004791:Enzyme Inhibitors; D009270:Naloxone; C063302:KN 62; D009020:Morphine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases