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

@article{Bazov2013TheEO,
  title={The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction},
  author={Igor Bazov and Olga Kononenko and Hiroyuki Watanabe and Vesna Kunti{\'c} and Daniil Sarkisyan and Malik Mumtaz Taqi and Muhammad Zubair Hussain and Fred Nyberg and Tatjana Yakovleva and Georgy Bakalkin},
  journal={Addiction Biology},
  year={2013},
  volume={18}
}
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… Expand
Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics
TLDR
Compared the expression levels and co-expression patterns of PDYN and KOR (OPRK1) genes in dorsolateral prefrontal cortex (dlPFC) between human alcoholics and controls, PDYN was found to be downregulated in dlPFC of alcoholics, while OPRK1 transcription was not altered. Expand
Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics
TLDR
Downregulation of opioid peptides in the dorsal striatum may contribute to development of alcoholism including changes in goal directed behavior and formation of a compulsive habit in alcoholics. Expand
Dynorphin and κ-Opioid Receptor Dysregulation in the Dopaminergic Reward System of Human Alcoholics
TLDR
Analysis of post-mortem NAc samples of human alcoholics to assess changes in prodynorphin (PDYN) and KOR (OPRK1) gene expression and co-expression (transcriptionally coordinated) patterns found differences in differences were not due to the decline in neuronal proportion in alcoholic brain and thereby represent transcriptional phenomena. Expand
Molecular mechanisms underlying increased PDYN and dynorphin expression in the prefrontal cortex of alcoholic men
TLDR
It is shown that prodynorphin is regulated by the transcriptional control protein repressor element 1 silencing transcription factor in vitro and that repressing transcription factor target gene and protein expression is altered in the prefrontal cortex of alcoholic men. Expand
Dissociable Effects of Kappa-Opioid Receptor Activation on Impulsive Phenotypes in Wistar Rats
TLDR
KOR activation was shown to induce an impulsive phenotype that was nor-BNI-sensitive, and this work demonstrated a dissociable effect of U50,488 on impulsive phenotypes related to intolerance to delay or response inhibition, with selective effects in the SSRT. Expand
Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder
TLDR
Results reveal whole-brain Diagnosis×PENK interactions on the neural response to errors and how this polymorphism-and potentially opioid neurotransmission more generally-modulates functioning and structural integrity of brain regions previously implicated in error-related processing. Expand
Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics
TLDR
The findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence. Expand
Voluntary Ethanol Intake Predicts κ-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques
TLDR
The strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism. Expand
The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors
TLDR
Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Expand
Long‐term ethanol effects on acute stress responses: modulation by dynorphin
TLDR
Data suggest that dynorphin plays an important role in the modulation of the brain stress‐response systems after chronic ethanol exposure, as well as determining the neuronal reactivity after foot shock exposure using c‐Fos immunoreactivity in limbic structures. Expand
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