Short predictable stress promotes resistance to anxiety behavior and increases dendritic spines in prefrontal cortex and hippocampus

Purpose: Some stress paradigms have shown protective effects of stress, suggesting increased resilience. Here we investigated whether a short predictable psychological stress, continuous or discontinuous, has a protective or negative long-lasting effect on behavior and cerebral morphology, and if there is difference when stress is experienced at different phases of neurodevelopment, namely in juvenile, adolescent, and adult rats.

Methods: Male and female rats were stressed on an elevated open platform at different ages (P23, P40, P75), and behavior was assessed later around 90 days of age. Behavioral analysis included measures of anxiety-like behavior, motor activity, and contextual memory. We also investigated the cerebral morphology by using dendritic spine analysis in pyramidal cells, in medial prefrontal cortex (Cg3), orbital prefrontal (AID) and hippocampal region CA1 as well as granule cells in the dentate gyrus (DG) of the hippocampus.

Results: Our results showed that short predictable psychological stress, continuous or discontinuous for 12 days, altered emotional behavior and neuronal morphology. Both behavioral and morphological results were sexually dimorphic and suggest a habituation and protective effect, as seen in the decrease of the anxiety-like behavior in the elevated plus maze (EPM), and an increase in excitatory synapse number, which is inferred from an increase of dendritic spines in the hippocampus and prefrontal cortex.

Conclusion: We conclude that the response to short predictable psychological stress induces a protective/positive effect in both sexes and at different developmental ages.