The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction

Authors

  • Igor Bazov,

    Corresponding author
    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
      Igor Bazov, Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124 Uppsala, Sweden. E-mail: igor.bazov@farmbio.uu.se
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  • Olga Kononenko,

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
    2. Department for Cellular Membranology of the Bogomoletz Institute of Physiology, Ukraine
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  • Hiroyuki Watanabe,

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
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  • Vesna Kuntić,

    1. Pharmaceutical Faculty, University of Belgrade, Serbia
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  • Daniil Sarkisyan,

    1. Department of Applied Mathematics, Financial University under the Government of the Russian Federation, Russia
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  • Malik M. Taqi,

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
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  • Muhammad Z. Hussain,

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
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  • Fred Nyberg,

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
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  • Tatjana Yakovleva,

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
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  • Georgy Bakalkin

    1. Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden
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Igor Bazov, Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124 Uppsala, Sweden. E-mail: igor.bazov@farmbio.uu.se

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.

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