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

Abstract

Heroin is a highly addictive drug that has led to the death of numerous people and caused tremendous economic, health-care, and societal costs. The mu opioid receptor gene (OPRM1) is a prominent candidate gene in the underlying neurobiology of heroin addiction. The OPRM1 undergoes extensive alternative splicing, generating multiple splice isoforms or variants that are conserved across species including rodents and humans (Pan, 2005; Pasternak & Pan, 2013). These splice variants can be categorized into three main types based on the predicted receptor structure: (a) Full-length 7 transmembrane (TM) C-terminal variants that are identical except for a different

Increased mu-opioid receptor expression is associated with reduced disease-free and overall survival in laryngeal squamous cell carcinoma

“…In comparison to control subjects, heroin users showed dysregulated expression of OPRM1 splice variant mRNAs in the medial prefrontal cortex, again suggesting that opioids could induce overexpression of MOR. 20 The impact of anaesthesia on the long-term prognosis of cancer patients who undergo surgery is increasingly recognised as important. However, these results are conflicting.…”

Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling

“…Although few studies have studied postmortem brains in subjects diagnosed with OUD, the approach has potential to uncover relevant and therapeutically viable pathways in the brain in opioid dependence. Previous work reported changes in opioid receptor expression in DLPFC (6)(7)(8) and altered expression of the machinery that regulates presynaptic glutamate release in NAc (9,10), potentially related to addiction severity in heroin users. Preclinical evidence has corroborated these findings by demonstrating unique interactions between opioid and glutamate receptor signaling in opioid withdrawal and dependence (11)(12)(13).…”

“…Although few studies have investigated postmortem brains in OUD, this approach has the potential to uncover clinically relevant pathways in opioid dependence. For example, previous work showed changes in opioid receptor expression in the DLPFC related to addiction severity in heroin users (6)(7)(8). Moreover, recent findings showed heroin users have altered expression of the presynaptic machinery regulating glutamate release in the NAc (9,10).…”

Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene, OPRM1: Insight into Complex Mu Opioid Actions

“…Altered expression of the OPRM1 splice variants were seen in multiple brain regions in a morphine tolerance mouse model [152], the human brain of HIV-infected individuals [153,154], and the medial prefrontal cortex of human heroin abusers and heroin self-administering rats [155]. Sex difference in expression of the Oprm1 variant mRNAs among the mouse brain regions was also observed [156].…”