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. 2018 Sep 17;8:13893. doi: 10.1038/s41598-018-31921-5

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Cocaine self-administration in adulthood. (A) Cocaine self-administration on a fixed-ratio 1 (FR1) schedule during daily 1-h sessions (n = 8). (B) WIN treatment in adolescence decreased the acquisition of cocaine self-administration in adulthood. Acquisition was defined as the first session during which the rat consumed at least 2.5 mg/kg cocaine (five lever presses) in 1 h. ^*p < 0.05 (Mantel-Cox survival analysis). (C) Progressive-ratio (PR) responding for cocaine after short access was unaffected by prior WIN treatment. The data are expressed as the mean ± SEM number of rewards (left y-axis) or breakpoint (right y-axis; n = 8). (D) Prior WIN treatment had no effect on the escalation of cocaine intake during daily 6-h self-administration sessions. ^*p < 0.05, ^***p < 0.001, ^****p < 0.0001, significant difference from baseline (one-way repeated-measures ANOVA followed by Bonferroni’s multiple-comparison post hoc test). (E) The first hour of the 6-h self-administration session (i.e., the loading phase) demonstrated the significant escalation of cocaine intake during 14 sessions compared with day 1 in both vehicle- and WIN-exposed rats. ^**p < 0.01 (Student’s two-tailed unpaired t-test). (F) Progressive-ratio (PR) responding for cocaine after long access (6 h) was unaffected by prior WIN treatment. The data are expressed as the mean ± SEM number of rewards (left y-axis) or breakpoint (right y-axis; n = 6).