Figure 4: Adolescent GD17-MAM rats are hyperactive, and have memory impairments with normal cognitive control.

A) MAM or an equal volume of saline is administered (i.p.) to a pregnant dam at gestational day 17 (GD17). The offspring are born on P0 and trained or exposed to the learning conditions during adolescence, starting at P35. Briefly, the rats are handled for five days prior to the start of testing. On P35, the rats are allowed to explore the arena for two 10-min trials. The following two days (eight 10-min trials/day) the rats are trained on the rotating arena to avoid the 60° shock zone that is stationary within the room. All trials have at least 10 min between them. At P60–70, the rats are tested in the same paradigm to assess cognitive behavior (see Figure 5 for these results). B) GD17-MAM rats make more errors (entries into the shock zone) on the first training day (Session 1: Treatment: F_1,17 = 5.74, p = 0.03; Trial: F7_,11 = 25.47, p < 0.0001; Interaction: F7_,11 = 3.98, p = 0.02), but perform asymptotically, similarly to control rats on the second day of training (Session 2: Treatment: F_1,17 = 2.62, p = 0.12; Trial: F7_,11 = 1.12, p = 0.42; Interaction: F7_,11 = 0.99, p = 0.48). C) GD17-MAM rats are hyperactive during all trials on both days (Session 1: Treatment: F_1,17 = 9.90, p = 0.01; Trial: F7_,11 = 2.26, p = 0.11; Interaction: F7_,11 = 1.33, p = 0.32. Session 2: Treatment: F_1,17 = 9.94, p = 0.01; Trial: F7_,11 = 1.30, p = 0.33; Interaction: F7_,11 = 0.26, p = 0.96). D) As with adult GD17-MAM rats, the hyperactivity accounts for the increased number of errors in adolescent GD17-MAM rats. When the number of errors is normalized to locomotor activity, learning performance is not different between GD17-MAM and control rats (Session 1: Treatment: F_1,17 = 2.25, p = 0.15; Trial: F_7,11 = 10.25, p < 0.001; Interaction: F7_,11 = 0.3358, p = 0.92. Session 2: Treatment: F_1,17 = 2.31, p = 0.15; Trial: F7_,11 = 0.87, p = 0.56; Interaction: F7_,11 = 0.62, p = 0.73). E) Within session memory was measured as the ability to increase the path to first enter the shock zone from trial-to-trial with the day’s session. Adolescent GD17-MAM rats have impaired within session memory acquisition during the first session (Session 1: Treatment: F_1,17 = 4.67, p = 0.05; Trial: F_7,11 = 4.26, p = 0.02; Interaction: F_7,11 = 1.14, p = 0.41), but are not different from controls during the second session (Session 2: Treatment: F_7,11 = 0.64, p = 0.43; Trial: F_7,11 = 2.41, p = 0.09; Interaction: F_7,11 = 0.82, p = 0.59). Across session memory was measured as the ability to increase the path to the first shock zone entrance across sessions 1 and 2 (Trial 1 and Trial 9, respectively). GD17-MAM rats have normal long-term memory (Treatment: F_7,11 = 2.20, p = 0.16; Trial: F_7,11 = 10.40, p = 0.01; Interaction: F_7,11 = 2.23, p = 0.15). Values are mean ± SEM. Control, n = 9. GD17-MAM, n = 10. *p < 0.05