Neonatal limited bedding and nesting experience may lead to a sex-dependent increase in panic-like defensive behaviours in adult mice

Abstract

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2–9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO₂ (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO₂ challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg⁻¹ i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg⁻¹ i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges.