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

TITLE=Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=9

YEAR=2015

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2015.00187

DOI=10.3389/fncel.2015.00187

ISSN=1662-5102

ABSTRACT=<p>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 (<italic>PDYN</italic>) and proenkephalin (<italic>PENK</italic>) 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 <italic>PDYN</italic> promoter variant rs1997794 associated with alcoholism affects <italic>PDYN</italic> expression. Postmortem specimens obtained from 24 alcoholics and 26 controls were included in final statistical analysis. <italic>PDYN</italic> mRNA and Met-enkephalin-Arg-Phe, a marker of PENK were downregulated in the caudate of alcoholics, while <italic>PDYN</italic> mRNA and Leu-enkephalin-Arg, a marker of <italic>PDYN</italic> 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.</p>