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The ?-opioid receptor nonsynonymous variant 118A>G is associated with prolonged abstinence from heroin without agonist treatment.

ABSTRACT: AIM:This study assesses whether opioid-related gene variants contribute to reduced vulnerability to relapse to heroin in persons who are not treated with ?-opioid receptor agonist. METHODS:Genotypes of 71 SNPs, in nine genes, were analyzed for association with long-term abstinence in former heroin-dependents of European/Middle Eastern ancestry, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 922). RESULTS:The functional OPRM1 nonsynonymous SNP rs1799971 (118A>G) showed significant association with long-term abstinence (Ppermutation = 0.03, dominant model, OR: 2.2; 95% CI: 1.5-3.3). CONCLUSION:Since the stress axis is regulated in part by ?-endorphin, this functional OPRM1 SNP may blunt the endogenous stress response and contribute to reduced vulnerability for relapse.

SUBMITTER: Levran O

PROVIDER: S-EPMC7270956 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The μ-opioid receptor nonsynonymous variant 118A>G is associated with prolonged abstinence from heroin without agonist treatment.

Levran Orna O Peles Einat E Randesi Matthew M da Rosa Joel Correa JC Adelson Miriam M Kreek Mary Jeanne MJ

Pharmacogenomics 20171004 15

<h4>Aim</h4>This study assesses whether opioid-related gene variants contribute to reduced vulnerability to relapse to heroin in persons who are not treated with μ-opioid receptor agonist.<h4>Methods</h4>Genotypes of 71 SNPs, in nine genes, were analyzed for association with long-term abstinence in former heroin-dependents of European/Middle Eastern ancestry, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 922).<h4>Results</h4>The functional OPRM1 nonsynonym ...[more]

PMID: 28976288

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Project description:Mu-opioid receptor agonists are clinically effective analgesics, but also produce undesirable effects that limit their clinical utility. The nociceptin opioid peptide (NOP) receptor system also modulates nociception, and NOP agonists might be useful adjuncts to enhance the analgesic effects or attenuate the undesirable effects of mu-opioid agonists. The present study determined behavioral interactions between the NOP agonist (-)-Ro 64-6198 and mu-opioid ligands that vary in mu-opioid receptor efficacy (17-cyclopropylmethyl-3,14β-dihyroxy-4,5α-epoxy-6α-[(3 ́-isoquinolyl)acetamindo]morphinan (NAQ) < buprenorphine < nalbuphine < morphine = oxycodone < methadone) in male rhesus monkeys. For comparison, Ro 64-6198 interactions were also examined with the kappa-opioid receptor agonist nalfurafine. Each opioid ligand was examined alone and following fixed-dose Ro 64-6198 pretreatments in assays of thermal nociception (n = 3-4) and schedule-controlled responding (n = 3). Ro 64-6198 alone failed to produce significant antinociception up to doses (0.32 mg/kg, IM) that significantly decreased rates of responding. All opioid ligands, except NAQ and nalfurafine, produced dose- and thermal intensity-dependent antinociception. Ro 64-6198 enhanced the antinociceptive potency of buprenorphine, nalbuphine, methadone, and nalfurafine. Ro 64-6198 enhancement of nalbuphine antinociception was NOP antagonist SB-612111 reversible and occurred under a narrow range of dose and time conditions. All opioid ligands, except NAQ and buprenorphine, produced dose-dependent decreases in rates of responding. Ro 64-6198 did not significantly alter mu-opioid ligand rate-decreasing effects. Although these results suggest that NOP agonists may selectively enhance the antinociceptive vs. rate-suppressant effects of some mu-opioid agonists, this small enhancement occurred under a narrow range of conditions dampening enthusiasm for NOP agonists as candidate "opioid-sparing" adjuncts.

Dataset Information

The ?-opioid receptor nonsynonymous variant 118A>G is associated with prolonged abstinence from heroin without agonist treatment.

Publications

The μ-opioid receptor nonsynonymous variant 118A>G is associated with prolonged abstinence from heroin without agonist treatment.

Similar Datasets

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