title: The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction.
abstract: The endogenous opioid system (EOS) plays a critical role in addictive processes. Molecular dysregulations in this system may be specific for different stages of addiction cycle and neurocircuitries involved and therefore may differentially contribute to the initiation and maintenance of addiction. Here we evaluated whether the EOS is altered in brain areas involved in cognitive control of addiction including the dorsolateral prefrontal cortex (dl-PFC), orbitofrontal cortex (OFC) and hippocampus in human alcohol-dependent subjects. Levels of EOS mRNAs were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and levels of dynorphins by radioimmunoassay (RIA) in post-mortem specimens obtained from 14 alcoholics and 14 controls. Prodynorphin mRNA and dynorphins in dl-PFC, κ-opioid receptor mRNA in OFC and dynorphins in hippocampus were up-regulated in alcoholics. No significant changes in expression of proenkephalin, and µ- and δ-opioid receptors were evident; pro-opiomelanocortin mRNA levels were below the detection limit. Activation of the κ-opioid receptor by up-regulated dynorphins in alcoholics may underlie in part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control.
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden. igor.bazov@farmbio.uu.se
authors.forename: Igor
authors.initials: I
authors.lastname: Bazov
authors.forename: Olga
authors.initials: O
authors.lastname: Kononenko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Vesna
authors.initials: V
authors.lastname: Kuntić
authors.forename: Daniil
authors.initials: D
authors.lastname: Sarkisyan
authors.forename: Malik M
authors.initials: MM
authors.lastname: Taqi
authors.forename: Muhammad Z
authors.initials: MZ
authors.lastname: Hussain
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.forename: Tatjana
authors.initials: T
authors.lastname: Yakovleva
authors.forename: Georgy
authors.initials: G
authors.lastname: Bakalkin
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000328:Adult; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D018847:Opioid Peptides / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D011957:Receptors, Opioid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012201:Reward; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000502:physiology
chemical_list: D004745:Enkephalins; D018847:Opioid Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; D004399:Dynorphins; C033660:preproenkephalin