Sex-Dependent Effects of Prenatal Stress on Learned Helplessness and Anxiety-Related Behaviours in Wistar Rats

There has been an increasing importance of studies that link sex to stress coping processes. Recently, we reported that male and female Wistar rats responded differently to prenatal stress (PS) under basal conditions. The aim of the present study was to determine the influence of sex on behaviour and coping strategies, as an effect of gestational adversity in rats that were exposed to an uncontrollable stressor. Once the animals reached adulthood, the offspring from stressed/nonstressed dams were subjected or not to antidepressant treatment with Sertraline. After that, they were exposed to a single inescapable shock (IS) session, in which the rats were further tested for escape behaviour along 10 days, as a model of learned helplessness (LH). In prenatally stressed animals after the IS, behavioural differences appeared in a sex specific manner. Males proved to be more susceptible to the adverse context than females, exhibiting behavioural despair in a large percentage of the cases. Surprisingly, PS did not affect shock escape failure, but did affect learning performance in a sex dependent manner. In females, PS led them to learn to avoid shocks, learning better than controls, and by contrast, PS males did not learn to avoid shocks and displayed some signs of anhedonia. Sertraline did not help animals to avoid shocks, but helped them to escape from it. Our data indicate the existence of sex dependent behavioural differences in PS animals when facing an uncontrollable stress situation, in which the changes induced by PS were not only different, but opposite between sexes. Corresponding author. I. Pereira-Figueiredo et al.