Fig. 6 NicA2-J1 prevents nicotine- and stress-induced reinstatement after extinguished nicotine intake. NicA2-J1 prevents nicotine- and stress-induced.

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Fig. 6 NicA2-J1 prevents nicotine- and stress-induced reinstatement after extinguished nicotine intake. NicA2-J1 prevents nicotine- and stress-induced reinstatement after extinguished nicotine intake. (A) Detailed timeline of the experiments. (B) Extinction phase. (C) Pretreatment with NicA2-J1 (10 mg/kg) prevented nicotine prime-induced reinstatement of nicotine-seeking behavior. The two-way mixed-factorial ANOVA, with group (PBS versus NicA2-J1) as the between-subjects factor and treatment (extinction, vehicle, and 0.03 mg/kg per injection of nicotine) as the within-subjects factor, showed a significant effect of treatment (F2,14 = 9.14, P = 0.0008) and a significant group × treatment interaction (F2,28 = 3.48, P = 0.044). The Newman-Keuls post hoc analysis revealed that one injection of nicotine (0.03 mg/kg per injection) significantly increased the number of lever presses compared with the extinction phase in PBS-treated rats (P < 0.0008). Nicotine priming did not induce the reinstatement of nicotine-seeking behavior in rats that were pretreated with NicA2-J1 during escalation (nicotine priming versus extinction, P = 0.61). The post hoc analysis showed that nicotine-induced priming was abolished in the NicA2-J1 group compared with the PBS group (nicotine priming in the PBS group versus nicotine priming in the NicA2-J1 group, P = 0.047). (D) Inactive lever responses were unaffected by nicotine infusions in either group (F2,28 = 0.64, P = 0.53). (E) NicA2-J1 (10 mg/kg) prevented the stress (yohimbine)–induced reinstatement of nicotine-seeking behavior in the PBS-pretreated group. The two-way mixed-factorial ANOVA, with group (PBS versus NicA2-J1) as the between-subjects factor and treatment (extinction, vehicle, and yohimbine) as the within-subjects factor, showed a significant effect of treatment (F2,14 = 3.31, P = 0.05) and a significant group × treatment interaction (F2,28 = 5.12, P = 0.0127). The Newman-Keuls post hoc analysis revealed that yohimbine significantly increased the number of lever presses in the PBS-pretreated group compared with the extinction phase (P = 0.011). No effect of yohimbine-induced reinstatement was observed in the NicA2-J1–pretreated group. (F) Inactive lever responses were unaffected by yohimbine in either group (F2,28 = 0.15, P = 0.85). *P < 0.05, **P < 0.01, versus extinction; &P < 0.05, nicotine priming–induced reinstatement between the PBS and NicA2-J1 groups. Marsida Kallupi et al. Sci Adv 2018;4:eaat4751 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).