Figure 5. The impact of early cognitive and control experience on adult cognitive ability in MAM rats.

The two-frame active place avoidance task was used to assess cognitive ability and memory in adult MAM rats that were either trained to perform the task during adolescence (AT) or exposed to the environmental conditions without shock (AE). At P60–70, the rats are trained for two days (eight 10-min trials/day) to avoid the 60° shock zone. On day three of training, the rats are given a 10-min retention trial with the shock on, followed by eight trials in which the shock zone is relocated 180°. We previously found that MAM rats are hyperactive and therefore our measures of spatial cognitive behavior take the distance walked by the rats into account. We estimated place avoidance as the number of entries made into the shock zone as a function of the distance walked on the arena (errors/distance). We estimated memory as the distance (path length) walked by the rats before the first entry into the shock zone. A) There were no group differences in place avoidance on Training Day 1, however there was an interaction between adolescent experience and trial (repeated measures MANOVA comparing the two treatments, and the two types of adolescent experience, across trials: Treatment: F_1,29 = 1.46, p = 0.23; Adolescent experience: F_1,29 = 6.74, p = 0.01; Trial: F_7,23 = 3.60, p = 0.01; Treatment x Adolescent experience: F_1,29 = 2.56, p = 0.12; Treatment x Trial: F_7,23 = 0.98, p = 0.47; Trial x Adolescent experience: F_7,23 = 2.66, p = 0.04; Treatment x Adolescent experience x Trial: F_7,23 = 1.52, p = 0.21). Because of this interaction, comparisons were made within each treatment condition (AT-control vs. AE- control and AT-MAM vs. AE-MAM). This revealed that AT-control rats performed significantly better than AE-control rats (Adolescent experience: F_1,14 = 8.79, p = 0.01; Trial: F_7,8 = 2.14, p = 0.15; Adolescent experience x Trial: F_7,8 = 5.77, p = 0.01) but that AT-MAM and AE-MAM rats were not different (Adolescent experience: F_1,15 = 0.50, p = 0.49; Trial: F_7,9 = 2.84, p = 0.07; Adolescent experience x Trial: F_7,9 = 0.72, p = 0.66). There was no group difference on Training Day 2, but there was a significant Treatment x Adolescent experience x Trial interaction (Treatment: F_1,29 = 0.34, p = 0.57; Adolescent experience: F_1,29 = 0.84, p = 0.37; Trial: F_7,23 = 3.46, p = 0.01; Treatment x Adolescent experience: F_1,29 = 1.28, p = 0.27; Treatment x Trial: F_7,23 = 0.67, p = 0.69; Adolescent experience x T rial: F_7,23 = 2.38, p = 0.06; Treatment x Adolescent experience x Trial: F_7,23 = 3.89, p = 0.01). Further analysis of this interaction revealed no significant effects between AT-control and AT-MAM rats (Treatment: F_1,15 = 2.58, p = 0.13; Trial: F_7,9 = 0.55, p = 0.78; Treatment x Trial: F_7,9 = 1.90, p = 0.18). Although it appears that there is an effect of trial between AE-control and AE-MAM rats on Training Day 2, significance was not reached (Treatment: F_1,14 = 0.10, p = 0.76; Trial: F_7,8 = 3.27, p = 0.06; Treatment x Trial: F_7,8 = 3.19, p = 0.06). There were no group differences in the retention trial (R) (Treatment: F_1,1 = 0.58, p = 0.45; Adolescent experience: F_1,1 = 0.34, p = 0.56; Treatment x Adolescent experience: F_1,1 = 3.77, p = 0.06) or during the conflict session (Treatment: F_1,29 = 0.57, p = 0.45; Adolescent experience: F_1,29 = 1.51, p = 0.23; Trial: F_7,23 = 7.83, p < 0.001; Treatment x Adolescent experience: F_1,29 = 0.37, p = 0.55; Treatment x Trial: F_7,23 = 0.83, p = 0.66; Adolescent experience x Trial: F_7,23 = 0.71, p = 0.66; Treatment x Adolescent experience x Trial: F_7,23 = 1.19, p = 0.34). B) Memory was assessed as the distance walked prior to the first entry into the shock zone. Control rats displayed a better memory, influenced by the adolescent experience; their distance walked before entering the shock zone for the first time was higher on Training day 1 (Treatment: F_1,29= 4.71, p = 0.04; Adolescent experience: F_1,29 = 7.06, p = 0.01; Trial: F_7,23 = 2.27, p = 0.07; Treatment x Adolescent experience: F_1,29 = 6.49, p = 0.02; Treatment x Trial: F_7,23 = 0.77, p = 0.62; Adolescent experience x Trial: F_7,23 = 0.69, p = 0.68; Treatment x Adolescent experience x Trial: F_7,23 = 0.53, p = 0.80). The significant interaction appears to be driven by the AT-control rats (AT-control vs. AT-MAM: Treatment: F_1,15 = 6.56, p = 0.02; Trial: F_7,9 = 2.20, p = 0.13; Treatment x Trial: F_7,9 = 0.91, p = 0.54) whereas the AE-control and AE-MAM groups were indistinguishable: Treatment: F_1,14 = 0.34, p = 0.57; Trial: F_7,8 = 2.36, p = 0.13; Treatment x Trial: F_7,8 = 0.97, p = 0.51). The AT-control was better than the AE-control group (Adolescent Experience: F_1,14 = 7.27, p = 0.02; Trial: F_7,8 = 0.72, p = 0.66; Adolescent Experience x Trial: F_7,8 = 0.63, p = 0.72) but the AT-MAM and AE-MAM groups were not different (Adolescent Experience: F_1,15 = 0.03, p = 0.88; Trial: F_7,9 = 2.02, p = 0.16; Adolescent Experience x Trial: F_7,9 = 1.62, p = 0.25). Performance was asymptotic by Day 2; there were no group differences in the path to first enter the shock zone on Training Day 2, during the retention test, or during the conflict session (Training Day 2: Treatment: F_1,29 = 0.54, p = 0.47; Adolescent experience: F_1,29 = 0.29, p = 0.59; Treatment x Adolescent experience: F_1,29 = 0.97, p = 0.33;_Trial: F_7,23 = 6.23, p = 0.0004;_Trial x Treatment: F_7,23 = 1.43, p = 0.24;_Trial x Adolescent experience: F_7,23 = 1.07, p = 0.41;_Trial x T reatment x Adolescent experience: F_7,23 = 2.34, p = 0.06. Retention (R): Treatment: F_1,29 = 0.38, p = 0.54; Adolescent experience: F_1,29 = 0.77, p = 0.39; Treatment x Adolescent experience: F_1,29 = 5.35, p = 0.03. Conflict: Treatment: F_1,29 = 0.00, p = 0.95; Adolescent experience: F_1,29 = 0.27, p = 0.61; Treatment x Adolescent experience: F_1,29 = 0.38, p = 0.54; Trial: F_7,23 = 3.36, p = 0.01; Trial x Treatment: F_7,23 = 1.51, p = 0.21; Trial x Adolescent experience: F_7,23 = 0.73, p = 0.65; Trial x Treatment x Adolescent experience: F_7,23 = 1.03, p = 0.44). A post hoc Tukey’s Honest Significant Difference test on the retention test did not reveal any significant adolescent experience differences among the groups. Data are presented as mean ± SEM. AT-control n = 8; AT-MAM n = 9; AE-control n = 8; AE-MAM n = 8. Significance was set to p < 0.05.