Neonatal handling alters learning in adult male and female rats in a task-specific manner.

We demonstrated that early life manipulations (neonatal isolation, neonatal handling, maternal separation) impaired fear conditioning in adult rats [Kosten, T.A., Miserendino, M.J.D., Bombace, J.C., Lee, H.J., Kim, J.J., 2005. Sex-selective effects of neonatal isolation on fear conditioning and foot shock sensitivity. Behav. Brain Res. 157, 235-244.; Kosten, T.A., Lee, H.J. and Kim, J.J., 2006. Early life stress impairs fear conditioning in adult male and female rats. Brain Res. 1087, 142-150.]. Although we found few effects on somatic responses to footshock, deficits in conditioned fear may reflect altered emotional reactivity to aversive stimuli not learning deficits. Here we test neonatal handling effects on learning and memory tasks that vary by aversive stimuli. Neonatal handling was chosen because it alters emotional reactivity in adult rats. Litters of Sprague-Dawley rats were assigned to neonatal handling (15-min separation from dam and nest on postnatal days 1-21) or control (nonseparated) conditions. Adult male and female rats with or without neonatal handling experience were compared on: (1) inhibitory avoidance that involves footshock; (2) a circular maze task that involves escape from bright light; and (3) object recognition that presumably does not involve aversive stimuli. Neonatal handling impaired inhibitory avoidance but enhanced object recognition. There were no differences in circular maze performance. In addition, sex differences emerged in both the inhibitory avoidance and object recognition tasks; female rats perform better in inhibitory avoidance and worse in object recognition compared to male rats. These data suggest that neonatal handling alters learning and memory in a task-specific manner that may reflect alterations in emotional reactivity or differential effects of the manipulation on unknown neurohormonal mechanisms.