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. 2018 Feb 21;9:731. doi: 10.1038/s41467-018-03087-1

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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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Fig. 1 — Treatment with cocaine or D-amphetamine impairs reversal learning. a Task design. b Systemic cocaine (10 mg/kg) or D-amphetamine (0.25 mg/kg) treatment did not alter the number of trials required to reach first reversal (one-way RM ANOVA, p = 0.55), but decreased the total number of reversals accomplished (ANOVA, p = 0.0037; post-hoc test versus saline, p = 0.0102 cocaine, p = 0.0197 D-amphetamine). c Treatment with cocaine or D-amphetamine did not alter perseverative behavior after a reversal (p = 0.46). d Lose-stay behavior was unaffected after cocaine or D-amphetamine treatment, both before (p = 0.21^†) and after (p = 0.77) the first reversal. Cocaine and D-amphetamine decreased win-stay behavior after (ANOVA, p = 0.0007; post-hoc test versus saline, p = 0.0009 for cocaine, p = 0.0336, D-amphetamine), but not before the first reversal (p = 0.67). Repeated measures from n = 25 animals. ^†Six animals had no losses before the first reversal, so the ANOVA was performed on data of n = 19 animals; graph shows n = 25. e We used a modified Rescorla–Wagner model to describe the behavior of the rats during reversal learning. f Example session. (Top) Simulated values of the nose pokes, given the rat’s optimal model parameters and observed choices. (Bottom) Modeled choice probabilities, converted from the simulated nose poke values using a softmax (unsmoothed), and the rat’s actual choice pattern (smoothed over 7 trials). g Best-fit learning parameters. Treatment with cocaine and D-amphetamine decreased α_loss, without affecting the other model coefficients (Wilcoxon matched-pairs signed rank test, *p = 0.032, **p = 0.0046, see Supplementary Table 2). h Simulating data with the model parameters extracted in g replicated the drug-induced effects of the behavioral data (n = 25 simulated rats; ANOVA trials to criterion, p = 0.86; total reversals, p = 0.0114, post-hoc test, p = 0.0411 for cocaine, and p = 0.0215 for D-amphetamine; ANOVA win-stay, p = 0.0090, post-hoc test, p = 0.0181 for cocaine and p = 0.0462 for D-amphetamine. ANOVA on all other measures, p > 0.1). Data shown as mean ± standard error of the mean; *p < 0.05, **p < 0.01, ***p < 0.001