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

Authorized Users Only
2013
Authors
Bazov, Igor
Kononenko, Olga
Watanabe, Hiroyuki
Kuntić, Vesna
Sarkisyan, Daniil
Taqi, Malik M.
Hussain, Muhammad Z.
Nyberg, Fred
Yakovleva, Tatjana
Bakalkin, Georgy
Article (Published version)
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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, ?-opioid receptor mRNA in OFC and dynorphins in hippocampus were up-regulated in alcoholics. No significant changes in expression of proenkephalin, and mu- and d-opioid receptors were evide...nt; pro-opiomelanocortin mRNA levels were below the detection limit. Activation of the ?-opioid receptor by up-regulated dynorphins in alcoholics may underlie in part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control.

Keywords:
Alcohol dependence / dynorphin / endogenous opioid system / human brain / -opioid receptor / prodynorphin
Source:
Addiction Biology, 2013, 18, 1, 161-169
Publisher:
  • Wiley-Blackwell, Hoboken
Projects:
  • Swedish Council for Working Life and Social Research (FAS)
  • AFA Forsakring
  • Swedish Science Research Council
  • Swedish Institute Visby Program

DOI: 10.1111/j.1369-1600.2011.00366.x

ISSN: 1355-6215

PubMed: 21955155

WoS: 000312740500016

Scopus: 2-s2.0-84871750715
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/1942
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