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. 2015 Mar;22(3):159–169. doi: 10.1101/lm.037770.114

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© 2015 Almeida-Corrêa et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Figure 4. — CsA impairs within-session extinction of contextual fear conditioning over multiple sessions. (A) Schematic representation of the protocol and mean time spent freezing (%) (±SEM) of mice treated with CsA (20 mg/kg) or vehicle (DMSO) 60 min prior to six daily 5-min extinction sessions. Line graphs show freezing levels for the first 3 min and the last 2 min of the session for each day of extinction, as well as for the 3 min of the test session. No difference between groups is found during the initial 3 min of the extinction sessions (n = 11 (CsA), 12 (DMSO); two-way repeated-measures ANOVA, P (drug) = 0.76, P (time) = 0.33, P (interaction) = 0.18). However, a significant difference is observed in the final 2 min of the sessions (two-way repeated-measures ANOVA, P (drug) = 0.009, P (time) = 0.27, P (interaction) = 0.67). Both groups show a similar degree of extinction when the initial 3 min of the first session are compared with the drug-free test session (two-way repeated-measures ANOVA; P (drug) = 0.82; P (time) = 0.0005; P (interaction) = 0.33; Student's t test for group comparison in the test session, P = 0.68). (B) Schematic representation of the protocol and mean time spent freezing (%) (±SEM) of mice treated with CsA (20 mg/kg) or vehicle (DMSO) 60 min prior to three daily 10-min extinction sessions. Line graphs show freezing levels for the first 3 min and the last 3 min of the session for each day of extinction, as well as for the 3 min of the test session. No difference between groups is observed during the initial 3 min of the extinction sessions, with a significant effect of time showing that extinction occurs over days (n = 5 (CsA), 7 (DMSO); two-way repeated-measures ANOVA, P (drug) = 0.70, P (time) = 0.04, P (interaction) = 0.27). At the end of the sessions, however, large differences in freezing are observed between the groups (two-way repeated-measures ANOVA, P (drug) = 0.0002, P (time) = 0.02, P (interaction) = 0.23; (*) P < 0.05, (**) P < 0.01, (***) P < 0.001, Bonferroni post hoc test). Both groups show similarly robust extinction when the initial 3 min of the first session are compared with the drug-free test session (two-way repeated-measures ANOVA; P (drug) = 0.96; P (time) = 0.002; P (interaction) = 0.73; Student's t test for group comparison in the test session, P = 0.71).