Figure 1.

Effect of relapse to fentanyl seeking after voluntary abstinence on Fos expression. A, Timeline of exp. 1. B, Self-administration: number of reinforced responses (food, 5 pellets/reinforcer delivery; fentanyl, 2.5 μg/kg/infusion) during the 6 h sessions. C, Choice during training: number of food-reinforced responses and fentanyl infusions earned during the 3 h choice sessions (20 trials/session), denoted by C1, C2, and C3 in B. D, Voluntary abstinence: number of food-reinforced responses and fentanyl infusions earned during the 3 h choice sessions (20 trials/session). E, Relapse test: number of active and inactive lever presses during 60 min test session (left) and the 20 min time course (right; n = 22 males, 20 females, between-subjects design). *p < 0.05, different from the inactive lever. F, Representative images of Fos+ cells in orbitofrontal and anterior insular cortex, at 10× magnification. Scale bar, 100 μm. G, Fos-IR quantification: number of Fos+ cells (counts/mm²). *p < 0.05, different from the no test group (n = 7/group, between-subjects design). Data are the mean ± SEM. For individual data, see Extended Data Figure 1-1.