Effects of prenatal restraint stress on the hypothalamus–pituitary–adrenal axis and related behavioural and neurobiological alterations

Abstract

Chronic hyper-activation of the hypothalamus-pituitary axis is associated with the suppression of reproductive, growth, thyroid and immune functions that may lead to various pathological states. Although many individuals experiencing stressful events do not develop pathologies, stress seems to be a provoking factor in those individuals with particular vulnerability, determined by genetic factors or earlier experience. Exposure of the developing brain to severe and/or prolonged stress may result in hyper-activity of the stress system, defective glucocorticoids-negative feedback, altered cognition, novelty seeking, increased vulnerability to addictive behaviour, and mood-related disorders. Therefore, stress-related events that occur in the perinatal period can permanently change brain and behaviour of the developing individual. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioural alterations including impaired feedback mechanisms of the HPA axis, disruption of circadian rhythms and altered neuroplasticity. Chronic treatments with antidepressants at adulthood have proven high predictive validity of the PRS rat as animal model of depression and, reinforce the idea of the usefulness of the PRS rat as an interesting animal model for the design and testing of new pharmacologic strategies in the treatment of stress-related disorders.