Fig. 4: Fentanyl occludes optogenetic mimicry of positive and negative reinforcement.
From: Distinct µ-opioid ensembles trigger positive and negative fentanyl reinforcement
a, Schematics for oGABAsi experiments (top) and histological validation (bottom). Scale bar, 1 mm. b, Fentanyl occlusion schedule during oGABAsi experiment. c, Active lever presses (ALP), inactive lever presses (ILP) and laser stimulations (LS) per minute during operant conditioning (n = 9 mice; LP: two-way repeated measures ANOVA, LP effect F(1,8) = 203, ***P < 0.001; session effect F(16,128) = 12.12, ***P < 0.001; LP × time interaction F(16,128) = 11.23, ***P < 0.001). Data are mean ± s.e.m. d, ALP and ILP during the pre-session (top) and during the session (bottom) after injection of fentanyl at different doses (n = 9 mice; LP pre-session: two-way repeated measures ANOVA, LP effect F(1,8) = 198.3, ***P < 0.001; time effect F(13,104) = 2.263, *P < 0.05; LP × time interaction F(13,104) = 2.586, *P < 0.05) Data are mean ± s.e.m. e, Laser stimulations per minute during the pre-session and post-session following intraperitoneal injection of saline or fentanyl at increasing doses (n = 9 mice). Data are mean ± s.e.m. f, Dose–response curve for fentanyl occlusion of oGABAsi (n = 9 mice). Sigmoid fit yielding an IC50 of 187.2 μg kg−1 and a Hill coefficient of −2.33. Data are mean ± s.e.m. g, Schematic of mouse preparation for optogenetic manipulation of CeA µOR-expressing neurons during an operant negative reinforcement task. h, Fentanyl occlusion schedule during the operant negative reinforcement task. i, ALP and ILP (top) and laser stop (bottom) rates during the FR1 and FR3 operant conditioning phases in control (n = 7 mice) or ChR2 (n = 8 mice) mice (ALP: two-way repeated measures ANOVA, group effect F(1,13) = 6.671, *P < 0.05; time effect F(19,247) = 4.64, ***P < 0.001; LP × time interaction F(19,247) = 2.59, ***P < 0.001; rate: two-way repeated measures ANOVA, group effect F(1,13) = 12.74, *P < 0.05; time effect F(19,247) = 6.059, ***P < 0.001; LP × time interaction F(19,247) = 3.801, ***P < 0.001). Data are mean ± s.e.m. j, ALP and ILP (left) and laser stop (right) after injection of fentanyl at different doses (n = 7 mice). Data are mean ± s.e.m. k, Dose–response curve for fentanyl occlusion of optogenetically manipulating CeA µOR-expressing neurons in an operant negative reinforcement task (n = 7 mice). Sigmoid fit yielding an IC50 of 70 μg kg−1 and a Hill coefficient of −1.94. Data are mean ± s.e.m.
