A single, prophylactic administration of prucalopride or PF-04995274 attenuates learned fear and decreases depressive-like behavior in male 129S6/SvEv mice. a Experimental design. b All mice exhibited comparable levels of freezing during CFC training. c, d (R,S)-ketamine (30 mg/kg), prucalopride (3 mg/kg), and PF-04995274 (10 mg/kg), but not prucalopride (10 mg/kg) or PF-04995274 (3 mg/kg), administration attenuated learned fear when compared with saline administration. e All groups of mice had comparable amounts of immobility during day 1 of the FST. f, g (R,S)-ketamine (30 mg/kg), prucalopride (3 mg/kg), and PF-04995274 (10 mg/kg), but not prucalopride (10 mg/kg) or PF-04995274 (3 mg/kg), significantly decreased immobility time during day 2 of the FST. h All groups of mice traveled a comparable amount of distance in the OF. i All groups of mice spent a comparable amount of time in the open arms of the EPM. j All groups of mice had a comparable number of entries into the open arms of the EPM. k, l All groups of mice had a comparable latency to approach the pellet in the NSF. m All groups of mice lost a comparable amount of weight following food deprivation for the NSF. (n = 5–10 male mice per group). Error bars represent ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001. Sal saline, K (R,S)-ketamine, Prucal prucalopride, PF PF-04995274, CFC contextual fear conditioning, FST forced swim test, OF open field, EPM elevated plus maze, NSF novelty suppressed feeding, min minutes, sec seconds, cm centimeters, no number, mg milligram, kg kilogram