title: Okadaic acid blocks the effects of 5-aza-2-deoxycytidine on consolidation, acquisition and retrieval of morphine-induced place preference in rats.
abstract: Recent studies indicated that epigenetic modification, especially DNA methylation, play an important role in the persistence of addiction-related memory. 5-aza-2-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases, was approved for clinical treatment. However, it is not clear whether 5-aza is involved in opiate addiction. In this study, using the morphine-induced conditioned place preference (mCPP) model in rats, we injected 5-aza into hippocampus (CA1) and prelimbic cortex (PL), and tested the behavioral consequences at various stages of consolidation, acquisition and retrieval. Moreover, to test whether protein phosphatase regulates the effects of 5-aza, protein phosphatase (PP) 1/2A inhibitor okadaic acid (OA) was infused before 5-aza injection. We found that 5-aza injection into CA1 but not into PL significantly attenuated the consolidation and acquisition of mCPP, however, the inhibition of DNA methylation in PL but not in CA1 enhanced the retrieval of mCPP. All these behavioral effects were absent when OA was infused before 5-aza injection. These findings suggest that 5-aza interfere opiate-related memory, and protein phosphatase plays an important role in this process.
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address: suin@psych.ac.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Sui
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy* / Q000503:physiopathology; D009294:Narcotics / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D009294:Narcotics; D019319:Okadaic Acid; D009020:Morphine; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: Conditioned place preference; DNA methylation; Hippocampus; Morphine addiction; Okadaic acid; Prelimbic cortex