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. 2019 Oct 9;5(10):eaay0351. doi: 10.1126/sciadv.aay0351

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Copyright © 2019 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).

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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Fig. 1 — (A) Schematic of experimental timeline for short- and extended-access self-administration and tissue collection during abstinence. (B) Self-administration training behavior for extended-access [AD1: two-way repeated-measures analysis of variance (ANOVA), treatment × session: F_9,190 = 4.724, P < 0.0001, n = 10 to 11 rats per group; AD30: two-way repeated-measures ANOVA, treatment × session: F_9,170 = 2.734, P = 0.005, n = 9 to 10 rats per group] and short-access (two-way repeated-measures ANOVA, treatment: F_1,90 = 198.8, P < 0.0001, n = 5 to 6 rats per group) paradigms. (C) Cocaine intake for short- and extended-access self-administration (g/kg per hour: t test, t₁₄ = 4.059, P = 0.001; g/kg per session: t test, t₁₄ = 10.87, P < 0.0001). (D) INO80 protein expression in NAc P1 fractions (AD1 after extended-access: t test, t₁₀ = 0.296, P = 0.773; AD30 after extended-access: t test, t₁₄ = 2.213, P = 0.044; AD30 after short-access: t test, t₉ = 0.792, P = 0.449; n = 5 to 8 rats per group). (E) Schematic of experimental timeline for extended-access self-administration, viral-mediated gene transfer, and cue-induced seeking test. (F) Extended-access self-administration training behavior before viral-mediated gene transfer for cocaine- (two-way repeated-measures ANOVA, treatment: F_2,26 = 0.274, P = 0.763, n = 9 to 10 rats per group) and saline-treated rats (F_1,9 = 0.139, P = 0.718, n = 4 to 7 rats per group). (G) Total active and inactive responses during a 60-min cue-induced seeking test on AD30 after extended-access self-administration for cocaine-treated rats [one-way ANOVA, lever × treatment F_2,26 = 7.361; Fisher protected least significant difference (PLSD) test for total active lever: GFP versus INO80, P = 0.018; GFP versus ΔNC-EQ, P = 0.018; n = 9 to 10 rats per group] and saline-treated rats (F_1,9 = 0.025; Fisher PLSD test for total active lever: GFP versus INO80, P = 0.92; n = 4 to 7 rats per group). Data are means ± SEM. *P < 0.05. s, saline; c, cocaine; EA, extended-access self-administration; SA, short-access self-administration; P1, nuclear fraction; ΔNC-EQ, catalytically inactive mutant INO80; a, active lever; i, inactive lever.