Fig. (6).

Rapastinel facilitates MPFC-dependent positive emotional learning and fear extinction in CUS-treated rats. (A) Mean ± SEM hedonic USVs in response to a conditioned stimuli that predicts heterospecific play 3 hrs post-dosing with Rapastinel (3 mg/kg, IV) or 0.9% sterile saline vehicle (1 ml/kg, IV) in 2-3 month old adult male SD rats exposed to a depressogenic regimen of chronic unpredictable stress (CUS; 2 stressors / day for 21 consecutive days) or non-stressed control rats (No CUS). A similar increase in PEL was seen in animals tested 2 weeks post-dosing. (B-C) Mean ± SEM % time freezing in CUS treated animals dosed with Rapastinel (3 mg/kg IV) or sterile saline vehicle (1 ml/kg IV) 1 hr before extinction day 1. Three shocks (0.5 mA, 1 s) were administered 90, 210, and 330 sec after animals were placed in the conditioning chamber on D0. During extinction, rats were submitted to a 5 min non-reinforced test trial every 24 hrs for 6 consecutive days (D1-6), and on day 14 post-conditioning (consolidation trial). Freezing was quantified via FreezeView software and was measured at baseline (30-60 sec) on D0, and during the last 3 min of each extinction trial. N = 9 - 14 rats per group. * P < .05 Fisher’s PLSD post hoc test vs. No CUS group (A-B), * P < .05 within subjects t-test, 2 tailed (C). Data adapted with permission from [29].