Anti-OPRM1 monoclonal antibody Made to order

Mu-opioid receptors (MORs) mediate the rewarding properties of oxycodone and other prescription opioid medications, which have played a central role in the current opioid epidemic in the United States. The human mu-opioid receptor gene (OPRM1) contains a functional single nucleotide polymorphism (SNP), A118G, which has been associated with altered opioid addiction risk, however the mechanisms responsible for this are not well understood. To explore this, we examined oxycodone conditioned place preference (CPP) and self-administration behavior (SA) in A112G mice, which possess a functionally analogous SNP in the mouse mu-opioid receptor gene (Oprm1). For CPP, male and female A112G mice homozygous for the A112 (wild-type; AA) or G112 (GG) allele were conditioned with doses of 1 and 3 mg/kg across an 8-day period. For SA, mice were allowed to self administer oxycodone (unit dose 0.25 mg/kg/infusion, FR1) for 4h/day for 10 consecutive days. We observed no effects of genotype or sex on conditioned place preference behavior. Oxycodone 3 mg/kg increased locomotor activity in AA mice but not GG mice, and both male and female GG mice self-administered significantly more oxycodone compared to their wild-type AA littermates. These studies suggest that the G allele promotes greater opioid intake, which may underlie greater opioid addiction morbidity in G-allele carriers.

Although the mechanism which regulates transcription in the 5'-UTR of the mu opioid receptor gene (OPRM1) in lymphocytes has been well-studied, a question remains as to whether there is post-transcriptional regulation of OPRM1 gene in lymphocytes. In this study, the authors describe both the role played by miRNAs and the impact of SIVmac239 infection on post-transcriptional regulation of OPRM1 gene in CEM x 174 cells. Our results show that miR-16 is able to bind the target site in the range of 8699-8719 nt from the stop codon in MOR-1 mRNA 3'-UTR and suppress the expression of OPRM1 gene. Mutation of this target site reduces the effect of miR-16. Morphine (1 mu M) inhibits the expression of miR-16, and this effect is reversed by the antagonist naloxone. Thus, morphine may up-regulate receptor level by both stimulating OPRM1 gene transcription and stabilizing its mRNA. SIVmac239 infection results in an apparent elevation of miR-16 and gradual reduction of OPRM1 gene expression. The inverse correlation of elevated miR-16 and reduced OPRM1 gene expression under viral loading confirmed the effect of SIVmac239 on post-transcriptional regulation of OPRM1 gene in lymphocytes. The authors conclude that miR-16 is a primary factor in post-transcriptional regulation of OPRM1 gene. SIVmac239 upregulates miR-16 levels and consequently suppresses OPRM1 gene expression. This finding will be helpful for full understanding of the regulatory mechanism of OPRM1 gene in lymphocytes, as well as the synergistic mechanism of HIV infection and morphine addiction in the pathogenesis of AIDS. (C) 2015 Wiley Periodicals, Inc.