Fig. 6: Pharmacological inhibition of MORs in the LPAG reduces HFD consumption.

a Schematics for the injection of AAV-DIO-eGFP into the LH of Penk-Cre mice. b Images showing eGFP expression in the LHPenk neuronal cells (left), and the high magnification image of a region in the white dashed box (right), replicated independently with similar results in 3 mice. Scale bar, 200 μm, 25 μm, respectively. fx, fornix. c eGFP-positive axons from LHPenk neuron were found in the VP, VTA, SN, PAG, and LPBN, replicated independently with similar results in 3 mice. Scale bars, 200 μm. ac, anterior commissure; IPN, interpeduncular nucleus; Aq, aqueduct. d Schematic for microinjections of CTAP into the LPAG of mice expressing mCherry or hM3D in the LHPenk neurons. Confocal image showing hM3D-expressing LHPenk neurons, replicated independently with similar results in 5 mice. Scale bar, 500 μm. e Images show the ___location of the cannula tips in the LPAG, replicated independently with similar results in 5 mice. Scale bars, 1 mm (top) and 200 μm (bottom). f, g 2.5 h food consumption (n = 8, 8, 6, 5 mice per group). In (f), one-way ANOVA (F(3,23) = 15.946, p < 0.001) was followed by Fisher LSD post hoc test for multiple comparisons; **p = 0.008, ***p < 0.001 compared with vehicle-mCherry mice; †††p < 0.001 compared with CTAP (1 μg)-hM3D mice. h Locomotor activity (n = 7, 6 mice per group). i Schematic for microinjection of veh or CTAP into the LPAG of PSS mice before HFD exposure. j 2.5 h HFD consumption test (n = 7, 6, 7 mice per group). One-way ANOVA (F(2,17) = 35.847, p < 0.001) was followed by Fisher LSD post hoc test for multiple comparisons; ***p < 0.001, †††p < 0.001 compared with PSS mice received vehicle. k–m Time spent (%) in the PSS-paired chambers (n = 7, 8 mice per group). Box–whisker plots display median and 2.5 to 97.5 percentiles of the distribution with whiskers extending from min to max values. In (l), two-tailed paired t test, t6 = 2.776, *p = 0.0322. In (m), two-tailed paired t test, t7 = 2.978, *p = 0.0206. n Locations of the cannula tips in the mice included in (l, m). Data are expressed as mean ± SEM.