Generation of the h/mOPRM1–118AA and h/mOPRM1–118GG lines is detailed in Supplementary Information. Insertion of sequence corresponding to human OPRM1 exon 1 is shown in Fig. 2C. Determination of the respective h/mOPRM1–118 genotype was carried out using the PCR method described for the human PET study. First generation h/mOPRM1–118AA and GG mice obtained from a cross of the founder lines were assessed with regard to overall health and behavior using an established testing battery 33. Table S2 shows that there were no genotype differences, with the exception of some excessive running in GG subjects upon introduction into the novel environment, and a modest but statistically significant increase in locomotion in h/m118AA males compared to h/m118GG males. Male mice aged 13–16 weeks were used for the binding, signaling experiments, and male mice aged 24 – 32 weeks were used for the microdialysis experiments.
