Extended Data Fig. 6: MOPR activation on LDRN^MOPR-mNAcSh is sufficient to enhance consummatory behavior.

a. Schematic of the Tail Immersion Test. Mice were tested at time 0, were injected with morphine (5mg/kg, s.c.), then tested every 10 min for up to 60 min, then again at 90 min. b. WT, Oprm1 KO, and Oprm1 KO x Penk-Cre rescue mice all show similar baseline responses at time 0. After morphine administration, WT mice significantly increase their latency to flick their tail, whereas Oprm1 KO and Oprm1 KO x Penk-Cre show no analgesic response to morphine mice (n = 5 WT, 2 Oprm1 KO, 6 Oprm1 KO x Penk-Cre rescue; WT/T0 vs Oprm1 KO/T0 p = 0.116, WT/T0 vs Oprm1 KO x Penk-Cre rescue/T0 p = 0.063, WT/T10 vs Oprm1 KO/T10 p < 0.001, WT/T10 vs Oprm1 KO x Penk-Cre rescue/T10 p < 0.001, WT/T90 vs Oprm1 KO/T90 p < 0.001, WT/T90 vs Oprm1 KO x Penk-Cre rescue/T90 p < 0.001). Statistical differences between WT and Oprm1 KO designated as (***) and differences between WT and Oprm1 KO x Penk-Cre rescue designated as (+++). c. Raster plots of individual licking events for one mouse, separated by trial. Only trials in which mice licked were included. d. Schematic of ChR2 experiments. e. Expression of EYFP-tagged ChR2 in LDRNPenk cell bodies (left, scale bar = 200 µm) and fiber placement in mNAcSh (right, scale bar = 200 µm). f. Penk-Cre- and Penk-Cre+ mice licked similar amounts for a sucrose solution in the ad libitum/No Laser condition. ChR2 photo-stimulation did not reduce licking (n = 7 Cre-, 6 Cre+). g. Penk-Cre- and Penk-Cre+ mice licked similar amounts for a sucrose solution in the WD/No Laser condition. By contrast, ChR2 photo-stimulation significantly reduced Cre+ licking, but not Cre- licking. h. Raster plots of individual licking events for one Penk-Cre+ mouse in the WD condition, separated by trial. Only trials in which mice licked were included. ChR2 photo-stimulation disrupted lick bout behavior compared to No Laser test days. All error bars represent ± SEM and n = biologically independent mice or cells (a). Post hoc p-values are derived from Two-way ANOVA with Sidak multiple comparisons (c, f, g).