The effects of prenatal stress on learning in adult offspring is dependent on the timing of the stressor.

Impaired fetal development has been linked with deficits in behavioural and emotional development during postnatal life. In order to investigate the mechanisms underlying this relationship, we studied the effect of acute stress at two different critical phases of pregnancy on cognitive function in adult guinea pig offspring. Pregnant guinea pigs were exposed to a psychological stressor (2h/day) on gestational days (gd) 50, 51, and 52 (PS50) or 60, 61, and 62 (PS60). Male offspring were grown to adulthood and tested in the Morris water maze (MWM) to assess spatial learning and memory. Latency, path length, swim speed and the strategy used to find the platform in each session of the MWM were measured. A reverse learning trial was performed where the platform was moved to a different area of the pool and the ability of the guinea pigs to learn a new platform position was assessed. There was no effect of stress at gd50 on latency to find the platform during any of the sessions in the MWM. PS60 male offspring exhibited enhanced development of a spatial strategy during sessions 3 and 4 of the MWM, but this was not associated with decreased latency. In the reversal task PS50 male offspring demonstrated use of non-spatial strategies to find the platform during the reversal task. This would suggest decreased retention of spatial memory in these animals. In contrast, control and PS60 male offspring demonstrated no bias to a particular strategy type. In conclusion, there are subtle effects of prenatal stress on spatial learning. PS60 offspring appear to exhibit enhanced spatial learning, while PS50 male offspring exhibit impaired spatial learning. These findings are consistent with those in humans, which indicate a strong effect of maternal anxiety during pregnancy on cognition in children, and that the timing of the maternal stress is critical to determining outcome. This model will allow us to determine the mechanisms that underlie the association between prenatal stress and altered learning strategy and ability.