title: Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus.
abstract: BACKGROUND
  The role of a nonsynonymous A118G polymorphism of the human micro-opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of naltrexone remains controversial. A functionally equivalent OPRM1 C77G polymorphism in rhesus macaques allows this to be addressed under controlled experimental conditions.
  
  
  METHODS
  Twenty-one rhesus macaques (13 female rhesus macaques, 8 male rhesus macaques) were genotyped for OPRM1 C77G and studied during 1-hour sessions for preference between an aspartame-sweetened alcohol solution (8.4% vol/vol) and a nonalcoholic control fluid in a baseline session followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced within-subject design.
  
  
  RESULTS
  Mixed-model analysis of variance controlling for baseline and sex showed a highly significant (p = .003) interaction between genotype and treatment. Post hoc analysis showed that vehicle-treated 77G carriers had markedly higher alcohol preference than 77C homozygous subjects (p = .001). Following naltrexone administration, 77G carriers decreased their preference (p = .002) and no longer differed from 77C homozygous subjects. In contrast, the latter group was unaffected by treatment and, in fact, showed a trend-level increase of preference following naltrexone.
  
  
  CONCLUSIONS
  These results support a critical pharmacogenetic role of OPRM1 variation for therapeutic efficacy of naltrexone.
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institutes of Health (NIH)/National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland 20892-1108, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Barr
authors.forename: Scott A
authors.initials: SA
authors.lastname: Chen
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Schwandt
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Lindell
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Suomi
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
mesh_terms: D000437:Alcoholism / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D000818:Animals; D001218:Aspartame / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005518:Food Preferences / Q000187:drug effects* / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000494:pharmacology* / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D013549:Sweetening Agents / Q000008:administration & dosage
chemical_list: D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D013549:Sweetening Agents; D009271:Naltrexone; D001218:Aspartame