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. 2022 Nov 11;13:6865. doi: 10.1038/s41467-022-34517-w

Fig. 5. Selective knockout of PVT µ-opioid receptors prevents heroin-induced behavioral disinhibition.

Fig. 5

a Surgical strategy for PVT µ-OR knockout with simultaneous optogenetic manipulation of PVT→NAc neurons. b Example images showing RNAscope in situ hybridization of PVT µ-ORs and κ-ORs in WT (top) and Oprm1fl/fl (bottom) mice. c Quantification reveals reduced µ-OR but not κ-OR RNA expression in Oprm1fl/fl mice (n = 3 Oprm1fl/fl, 2 WT mice; two-way ANOVA, group x receptor interaction: F1,32 = 7.61, P = 0.01; Sidak’s post-hoc: P = 0.001). d–f Knockout of PVT µ-ORs in Oprm1fl/fl mice rescued the suppression of sucrose self-administration caused by optogenetic stimulation of PVT→NAc neurons (d), TMT (e), and yohimbine (f) despite systemic heroin injection (n = 6–8 mice/group; Opto: n = 6 Oprm1fl/fl, 8 WT mice; repeated-measures two-way ANOVA, group × day interaction: F2,24 = 8.33, P = 0.002; Sidak’s post-hoc: opto + heroin P = 0.001; TMT: n = 6 Oprm1fl/fl, 8 WT mice; repeated-measures two-way ANOVA, group × day interaction: F2,24 = 8.94, P = 0.001; Sidak’s post-hoc: TMT + heroin P = 0.001; yohimbine: n = 6 Oprm1fl/fl, 8 WT mice; repeated-measures two-way ANOVA, group × day interaction: F2,24 = 5.53, P = 0.01; Sidak’s post-hoc: TMT + heroin P = 0.02). µ-OR µ-opioid receptor, κ-OR κ-opioid receptor, Base Baseline, Opto optogenetics, Yoh Yohimbine. Group comparisons: *P < 0.05, **P < 0.01, ***P = 0.001. Bar graphs are presented as mean values ± SEM. Source data are provided as a Source Data file.