a. Schematic of Oprm1 KO x Penk-Cre rescue of MOPRs in LDRN. b. In situ micrograph (left; Oprm1, Penk, Cre) and associated fluorescent micrograph (right; GFP-tagged viral vector) of DRN in an Oprm1 KO x Penk-Cre+ mouse (scale bar = 200 μm). c. Quantification of b. d.
Oprm1 KO x Penk-Cre+ mice (red) show restored FD intake compared to Cre− (blue) mice (n = 8 Cre−, 11 Cre+). e. Morphine conditioned place preference (CPP) assay. (top) Schematic of CPP procedure. (bottom left) Heat map of time spent in each chamber during pretest and posttest. Warmer colors indicate more time spent in that area. (bottom right) Wildtype and Oprm1 KO x Penk-Cre+ (red) mice spent more time in the morphine paired side compared to Cre− (blue) mice (n = 6 WT, 8 Cre−, 8 Cre+). f. Schematic of opto-MOR experiments. g. Expression of EYFP-tagged opto-MOR in LDRNPenk (left, scale bar = 200 μm) and fiber placement (red dashed line) in mNAcSh (right, scale bar = 200 μm). Zoomed in image shows labeled nuclei in DRN. h. Saline/No Laser treated mice licked more compared to the naloxone/No Laser treated test day. Opto-MOR stimulation restored licking after naloxone injections (n = 8). All error bars represent ± SEM and n = biologically independent mice. Medians are in orange. Post hoc p-values are derived from One-way (d) or Two-way ANOVA with Sidak multiple comparisons (c, g,
Extended Data Table 4).