Mouse model of OPRM1 (A118G) polymorphism has altered hippocampal function.

Published

Journal Article

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 altered phenotypes, we used a mouse model possessing the equivalent nucleotide/amino acid substitution in the Oprm1 gene. In order to investigate the impact of this SNP on circuit function, we used voltage-sensitive dye imaging in hippocampal slices and in vivo electroencephalogram recordings of the hippocampus following MOPR activation. As the hippocampus contains excitatory pyramidal cells whose activity is highly regulated by a dense network of inhibitory neurons, it serves as an ideal structure to evaluate how putative receptor function abnormalities may influence circuit activity. We found that MOPR activation increased excitatory responses in wild-type animals, an effect that was significantly reduced in animals possessing the Oprm1 SNP. Furthermore, in order to assess the in vivo effects of this SNP during MOPR activation, EEG recordings of hippocampal activity following morphine administration corroborated a loss-of-function phenotype. In conclusion, as these mice have been shown to have similar MOPR expression in the hippocampus between genotypes, these data suggest that the MOPR A118G SNP results in a loss of receptor function.

Full Text

Duke Authors

Cited Authors

  • Mague, SD; Port, RG; McMullen, ME; Carlson, GC; Turner, JR

Published Date

  • October 2015

Published In

Volume / Issue

  • 97 /

Start / End Page

  • 426 - 435

PubMed ID

  • 25986698

Pubmed Central ID

  • 25986698

Electronic International Standard Serial Number (EISSN)

  • 1873-7064

Digital Object Identifier (DOI)

  • 10.1016/j.neuropharm.2015.04.032

Language

  • eng

Conference Location

  • England