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OPRM1 :red_flag:opioid receptor mu1 gene (sleep quality and OPRM1…

- - - - either a reduction in efficacy of endogenous MOPR modulation of GABA activity
      - or, alternatively, a reduction in endogenous opioidergic tone in G/G animals
    - - found significant reductions in the female responses to MOPR activation compared to males, regardless of genotype.
      - more efficacious in males compared to females in the analgesic properties of opioids
      - In contrast, female rats respond more robustly to the rewarding properties of opioids and women are more likely to abuse prescription opioid analgesics .Specifically in the hippocampus, ovarian steroid hormones have been shown to influence levels of opioid peptides and the availability of MOPRs on the surface of PV cells
      - did not demonstrate interactions between genotype and sex. --> differences in CA1 responses to MOPR activation may not directly underlie the sex-specific reduction in morphine-conditioned place-preference studies
    - - an alteration in hippocampal function as a result of the Mu Opioid Receptor SNP, A112G, and the reduced effect of DAMGO and morphine in G/G animals further supports a loss-of-function of the MOPR as a consequence of this SNP
      - the strong disinhibition controlled by MOPRs on interneurons of the hippocampus is absent, therefore leading us to conclude that this polymorphism represents a “loss of function” phenotype in the context of hippocampal microcircuitry
      - the loss of function in our microcircuitry model occurs due to the reduced inhibitory drive onto pyramidal cells
      - these results suggest deficits in the early stages of binding and signal transduction and would be consistent with the immediate changes seen after acute MOPR agonist administration.
      - SNP in mice identified reduced function in the absence of reduced expression
      - the probable mechenisims
        
        functional reduction of voltage-gated Ca2+ activation following morphine administration in isolated sensory neurons from G/G animals consistent with a loss of function of the receptor.
        
        A112G mouse line, a reduction in GTP.S binding was detected in
        several brain regions
        
        In human positron emission topography studies have demonstrated a decreased binding potential of [11C]carfentanil, indicating a reduced MOPR availability, in those with the G allele.