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Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior
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Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior
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Journal Article
Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior
2009
Overview
A single nucleotide polymorphism (SNP) in the human μ-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanisms underlying these associations remain elusive. To clarify the functional mechanisms linking the OPRM1 A118G SNP to addiction and analgesia phenotypes, we derived a mouse model possessing the equivalent nucleotide/amino acid substitution in the Oprm1 gene. Mice harboring this SNP (A112G) demonstrated several phenotypic similarities to humans carrying the A118G SNP, including reduced mRNA expression and morphine-mediated antinociception. We found additional phenotypes associated with this SNP including significant reductions of receptor protein levels, morphine-mediated hyperactivity, and the development of locomotor sensitization in mice harboring the G112 allele. In addition, we found sex-specific reductions in the rewarding properties of morphine and the aversive components of naloxone-precipitated morphine withdrawal. Further cross-species analysis will allow us to investigate mechanisms and adaptations present in humans carrying this SNP.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ alleles
/ Analgesics, Opioid - pharmacology
/ Animals
/ Conditioning, Operant - drug effects
/ Effects
/ Enkephalin, Ala-MePhe-Gly- - metabolism
/ Female
/ Genes
/ Genotype
/ Humans
/ Male
/ Mice
/ Morphine
/ Motor Activity - drug effects
/ Pain
/ Polymorphism, Single Nucleotide
/ Receptors, Opioid, mu - genetics
/ Receptors, Opioid, mu - metabolism
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA
/ Rodents
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