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2297 – Dysregulation Of The Endogenous Opioid System In The Brain Of Human Alcoholics

Published online by Cambridge University Press:  15 April 2020

G. Bakalkin ,
I. Bazov ,
Z. Hussain ,
D. Sarkisyan ,
H. Watanabe ,
O. Kononenko ,
V. Karpyak  and
T. Yakovleva
G. Bakalkin
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
I. Bazov
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
Z. Hussain
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
D. Sarkisyan
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
H. Watanabe
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
O. Kononenko
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
V. Karpyak
Affiliation:
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
T. Yakovleva
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

Abstract

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Introduction

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.

Aims

We here 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), anterior insula (AI) and hippocampus, in human alcohol dependent subjects.

Methods

Levels of EOS mRNAs were measured by qRT-PCR, and levels of dynorphins by radioimmunoassay in postmortem human specimens.

Results

Prodynorphin kappa-opioid receptor mRNAs and dynorphins were upregulated or demonstrated higher dispersion in alcoholics.

Conclusions

Dysregulation in the kappa-opioid receptor/dynorphin system in alcoholics may contribute to alcohol craving and neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control.

Acknowledgements

We are grateful to the NSW Tissue Resource Centre for providing human brain samples. Supported by the Swedish VR and FAS.

Type
Abstract
Information
European Psychiatry , Volume 28 , Issue S1: Abstracts of the 21th European Congress of Psychiatry , 2013 , 28-E1440
Copyright
Copyright © European Psychiatric Association 2012
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