Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self‐administering male rats

Heroin, a mu agonist, acts through the mu opioid receptor. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating an array of splice variants that are conserved from rodent to humans. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically...

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Bibliographic Details
Published in:Journal of neuroscience research 2022-01, Vol.100 (1), p.35-47
Main Authors: Brown, Taylor G., Xu, Jin, Hurd, Yasmin L., Pan, Ying‐Xian
Format: Article
Language:English
Subjects:
Addictions
Alternative Splicing
Analgesia
Animals
Decision making
Drug abuse
Drug tolerance
Heroin
Humans
Intravenous administration
Male
Males
medial prefrontal cortex
mu opioid receptor
Narcotics
opioid
Opioid receptors (type mu)
OPRM1
Pain perception
Prefrontal cortex
Prefrontal Cortex - metabolism
Rats
Receptors
Receptors, Opioid, mu - genetics
RNA, Messenger - metabolism
Rodents
splicing
Substance-Related Disorders - genetics
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Summary:Heroin, a mu agonist, acts through the mu opioid receptor. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating an array of splice variants that are conserved from rodent to humans. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating various actions of mu opioids, including analgesia, tolerance, physical dependence, rewarding behavior, as well as addiction. In the present study, we examine expression of the OPRM1 splice variant mRNAs in the medial prefrontal cortex (mPFC), one of the major brain regions involved in decision‐making and drug‐seeking behaviors, of male human heroin abusers and male rats that developed stable heroin‐seeking behavior using an intravenous heroin self‐administration (SA) model. The results show similar expression profiles among multiple OPRM1 splice variants in both human control subjects and saline control rats, illustrating conservation of OPRM1 alternative splicing from rodent to humans. Moreover, the expressions of several OPRM1 splice variant mRNAs were dysregulated in the postmortem mPFCs from heroin abusers compared to the control subjects. Similar patterns were observed in the rat heroin SA model. These findings suggest potential roles of the OPRM1 splice variants in heroin addiction that could be mechanistically explored using the rat heroin SA model. Dysregulated expression of several OPRM1 splice variant mRNAs in the medial prefrontal cortex of male human heroin abusers was recaptured in heroin self‐administering male rats, suggesting potential roles of the OPRM1 splice variants in heroin addiction that could be mechanistically explored using the rat heroin self‐administration model.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.24640