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The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction
Author(s) -
Bazov Igor,
Konko Olga,
Watanabe Hiroyuki,
Kuntić Vesna,
Sarkisyan Daniil,
Taqi Malik M.,
Hussain Muhammad Z.,
Nyberg Fred,
Yakovleva Tatjana,
Bakalkin Georgy
Publication year - 2013
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2011.00366.x
Subject(s) - dynorphin , proenkephalin , nociceptin receptor , addiction , neuroscience , opioid peptide , hippocampus , orbitofrontal cortex , endogenous opioid , opioid , prefrontal cortex , psychology , receptor , medicine , cognition
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.