title: Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus.
abstract: Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of α and β isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both α and β isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either α and β CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors.
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kadivar
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; Electrophysiology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mfarahmandfar@razi.tums.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Farahmandfar
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Faezeh Esmaeli
authors.initials: FE
authors.lastname: Ranjbar
authors.affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D007527:Isoenzymes; D009292:Narcotic Antagonists; D009294:Narcotics; D012333:RNA, Messenger; D009270:Naloxone; D009020:Morphine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Behavioral sensitization; CaMKII; Hippocampus; Morphine; Rat