Reducing Behavioral Inhibition to Novelty via Systematic Neonatal Novelty Exposure: The Influence of Maternal Hypothalamic-Pituitary-Adrenal Regulation

Abstract

Behavioral inhibition (BI) to novelty is thought to be a stable temperament type that appears early in life and is a major risk factor for anxiety disorders. In the rat, habituation of such inhibition can be facilitated via neonatal novelty exposure (NNE), thus reducing BI to novelty. Here, we tested the hypothesis that this early intervention effect is modulated by the context of maternal self-stress regulation. The NNE was carried out during postnatal days 1-21, in which one half of each litter was exposed to a relatively novel nonhome environment for 3-min daily while the remaining one half stayed in the home cage. After weaning, BI to novelty was assessed in an open field with a measure of disinhibition defined as a greater increase in exploration across two brief trials. Maternal context was characterized by trait measures of hypothalamic-pituitary-adrenal (HPA) axis reactivity, including basal and stress-evoked corticosterone (CORT) responses. Family-to-family variations in the NNE effect were associated with variations in maternal HPA function-a low-basal CORT and high-evoked CORT response profile constituting the context for a novelty-induced facilitation of disinhibition (i.e., a greater increase in exploratory activity over repeated trials) and an opposite HPA profile constituting the context for a novelty-induced reduction of disinhibition. This result is consistent with the hypothesis that maternal self-stress regulation modulates the effect of early life intervention on BI to novelty and suggests that effective interventions should include strategies to help mothers improve their self-stress regulation.