Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics.

Daniil Sarkisyan,Igor Bazov,Olga Kononenko,Georgy Bakalkin,Xingwu Zhou,Olga Yamskova,Victor M Karpyak,Hiroyuki Watanabe,Tatiana Yakovleva,Muhammad Z Hussain,Oleg Krishtal

doi:10.3389/fncel.2015.00187

Daniil Sarkisyan, Igor Bazov + Show 9 more

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https://doi.org/10.3389/fncel.2015.00187

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Abstract

The endogenous opioid peptides dynorphins and enkephalins may be involved in brain-area specific synaptic adaptations relevant for different stages of an addiction cycle. We compared the levels of prodynorphin (PDYN) and proenkephalin (PENK) mRNAs (by qRT-PCR), and dynorphins and enkephalins (by radioimmunoassay) in the caudate nucleus and putamen between alcoholics and control subjects. We also evaluated whether PDYN promoter variant rs1997794 associated with alcoholism affects PDYN expression. Postmortem specimens obtained from 24 alcoholics and 26 controls were included in final statistical analysis. PDYN mRNA and Met-enkephalin-Arg-Phe, a marker of PENK were downregulated in the caudate of alcoholics, while PDYN mRNA and Leu-enkephalin-Arg, a marker of PDYN were decreased in the putamen of alcoholics carrying high risk rs1997794 C allele. 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.

Highlights

The endogenous opioid peptides dynorphins and enkephalins and their receptors have a critical role in drug and alcohol dependence (Shippenberg et al, 2007; Wee and Koob, 2010; Butelman et al, 2012)
Analyzing demographic and clinical data and tissue characteristics t-test showed no significant differences in age [t(45) = 0.084, p = 0.93], post-mortem interval (PMI) [t(47) = 0.95, p = 0.35], brain pH values [t(46) = −0.91, p = 0.37], RNA quality indicator (RQI) [t(46) = −0.99, p = 0.32] and Firsher’s exact test showed no significant difference in number of smokers between alcoholics and controls
To examine whether the endogenous opioid peptide system undergoes adaptive changes in the striatum of human alcoholics we analyzed the levels of PDYN and PENK mRNA, PDYNderived Dynorphin A (Dyn A), dynorphin B (Dyn B) and LER, and PENK-derived MEAP in post-mortem samples of the caudate and putamen of alcoholics (24 subjects) and controls (26 subjects)

Summary

Introduction

The endogenous opioid peptides dynorphins and enkephalins and their receptors have a critical role in drug and alcohol dependence (Shippenberg et al, 2007; Wee and Koob, 2010; Butelman et al, 2012). Animal studies propose that drug/alcohol induced changes in prodynorphin (PDYN) and proenkephalin (PENK) expression underlie neuroplastic adaptations critical for addiction (Shippenberg et al, 2007; Walker and Koob, 2008; Wee and Koob, 2010; Butelman et al, 2012). These changes may be brain-area specific, and may differentially contribute to specific stages of an addiction cycle (Yuferov et al, 2009; Butelman et al, 2012; Bazov et al, 2013).

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