RGD Reference Report - Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol. - Rat Genome Database

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Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol.

Authors: Ashenhurst, James R  Bujarski, Spencer  Ray, Lara A 
Citation: Ashenhurst JR, etal., Pharmacol Biochem Behav. 2012 Dec;103(2):253-9. doi: 10.1016/j.pbb.2012.08.019. Epub 2012 Aug 27.
RGD ID: 402528370
Pubmed: PMID:22954510   (View Abstract at PubMed)
PMCID: PMC3683577   (View Article at PubMed Central)
DOI: DOI:10.1016/j.pbb.2012.08.019   (Journal Full-text)

Naltrexone, one of four FDA-approved pharmacotherapies for alcohol dependence, has shown moderate efficacy in clinical trials. Pharmacogenetic effects have been reported such that allelic variation at the gene encoding the mu-opioid receptor (OPRM1, rs1799971) predicts naltrexone-induced blunting of the positively reinforcing effects of alcohol. However, naltrexone also binds, albeit to a lesser degree, to kappa and delta opioid receptors in the brain. This alternate binding presents the possibility that single nucleotide polymorphisms (SNPs) in the kappa and delta opioid receptor (OPRK1 and OPRD1) genes may contribute to naltrexone pharmacogenetics. Therefore, the goal of this exploratory study was to re-examine data from a double-blind placebo controlled laboratory trial of naltrexone for pharmacogenetic effects at kappa and delta opioid receptor tag SNPs. Participants were 40 heavy drinkers (12 female) who underwent an intravenous alcohol challenge paradigm after receiving naltrexone (50mg) or placebo in randomized and crossover fashion. Dependent variables were self-reported alcohol-induced stimulation, sedation, and craving. Multilevel models revealed a significant Naltrexone×OPRK1 Genotype (rs997917) interaction predicting alcohol-induced sedation, such that TT homozygotes reported lower naltrexone-induced alcohol sedation as compared to carriers of the C allele. Moreover, there was a significant Naltrexone×OPRD1 Genotype (rs4654327) interaction predicting alcohol-induced stimulation and craving, such that carriers of the A allele at this locus reported greater naltrexone-induced blunting of alcohol stimulation and alcohol craving compared to GG homozygotes. These findings suggest that additional pharmacogenetic effects in the opioid receptor system may account for individual differences in response to naltrexone in the human laboratory.



Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OPRD1HumanAddictive alcohol use treatmentIAGP associated with alcohol dependence more ...RGD 
OPRK1HumanAddictive alcohol use treatmentIAGP associated with alcohol dependence more ...RGD 
OPRD1HumanAmeliorated by exposure to medication treatmentIAGP associated with alcohol dependence more ...RGD 
OPRK1HumanAmeliorated by exposure to medication treatmentIAGP associated with alcohol dependence more ...RGD 
OPRD1HumanMedication history treatmentIAGP associated with alcohol dependence more ...RGD 
OPRK1HumanMedication history treatmentIAGP associated with alcohol dependence more ...RGD 
Objects Annotated

Genes (Homo sapiens)
OPRD1  (opioid receptor delta 1)
OPRK1  (opioid receptor kappa 1)


Additional Information