Susceptibility to opioid addiction is associated with variants in the gene encoding the MOR, <i>OPRM1</i> Varying with ethnicity, ∼25% of humans carry a single nucleotide polymorphism (SNP) in <i>OPRM1</i> (A118G).
The OPRM1rs1799971" genes_norm="4988">A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the rs1799971" genes_norm="4988">N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
Mu opioid (MOP) receptors are the primary molecular target of opiates but increasing evidence support in vivo functional heteromerization with the delta opioid (DOP) receptor, which may be part of the neurobiological processes underlying opiate addiction.
Altogether, these data suggest that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo through modulating MOR expression, as well as AMPA GluR1-S845 phosphorylation, which might be one of the mechanisms underlying the development of opiate addiction.
Buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor (KOR) antagonist, is an emerging therapeutic agent for maternal opioid dependence in pregnancy and neonatal abstinence syndrome.
Methadone is a synthetic μ-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence.
To study a possible involvement of this μ-OR regulator in opiate dependence, the present study assessed by Western blot analysis the contents of IRAS/nischarin and μ-OR in total homogenates and subcellular preparations of postmortem human prefrontal cortex (PFC/BA9) of long-term opiate and mixed opiate/cocaine abusers as well as of matched healthy control subjects.
In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68.0 mg, s.d.=30.1 mg) and rs73568641 (P=2.8 × 10<sup>-8</sup>), the nearest gene (306 kilobases) being OPRM1.
No opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility.
Single-nucleotide polymorphisms (SNPs) in the μ-opioid receptor (OPRM1), multidrug resistance (ABCB1), and catechol-o-methyltransferase (COMT) genes are associated with risk for opioid addiction in adults.
Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL, ABCB1, OPRM1) with opioid dependence in European population: a case-control study.
This study aimed to investigate the associations between response to methadone maintenance treatment (MMT) and polymorphisms in genes coding for the OPRM1 opioid receptor, the metabotropic glutamate receptors GRM6 and GRM8, the nuclear receptor NR4A2, the photolyase enzyme cryptochrome 1 (CRY1), and the transcription factor myocardin (MYOCD), which have previously been associated with the risk of opioid dependence disorder.
Therefore, our data provide no support for the idea that variations in OPRM1, OPRD1, PENK and POMC are associated with alcohol dependence or general illicit drug dependence, but variations in PENK and POMC appear to be associated with the narrower phenotype of opioid dependence in these families.
Although a role of OPRM1 polymorphisms in determining risk for opioid dependencecannot be entirely discounted, a major contribution of the Asn40Asp polymorphism seems unlikely.
In MOP receptor-overexpressing sc2 cells, short-term morphine exposure was found to be much more potent and efficacious in inhibiting forskolin-elicited production of cAMP, and long-term morphine exposure was shown to induce a substantially higher degree of opiate dependence, as reflected by adenylate cyclase sensitization, than it did in wild-type neuroblastoma cells.
Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample.