Can the Behaviour Abnormalities Induced by Gestational Stress in Rats be Prevented or Reversed?

Abstract

Gestational stress increases circulating maternal hormones that produce changes in behaviour and impair the feedback regulation of the hypothalamic pituitary adrenal axis of the offspring. Prenatally-stressed (PS) rats also release more corticotropin-releasing hormone (CRH) in the limbic system in response to stimulation than controls. This contributes to their exaggerated fear of intimidating situations and depressive-like behaviour. By using different treatments given to the pregnant mother, to neonatal or adult offspring, it has been possible to learn more about the mechanisms underlying the behavioural abnormalities induced by gestational stress. Many of these treatments were also able to prevent or reverse the abnormalities. They included maternal adrenalectomy and replacement of her basal hormone levels to avoid the prolonged elevation of plasma corticosterone, administration of anti-anxiety agents to reduce her reactions to the stress and continuous blockade of opioid receptors to prevent down-regulation of the foetal opioid system and subsequent alterations in behaviour. Hyperanxiety in the adult PS offspring could also be avoided if, as neonates, they were handled daily for 10 days, or given an antidepressant, amitriptyline for 4-5 weeks in the prepubertal period. Increased fear of novelty in adult PS rats could also be abolished by the intracerebro-ventricular administration of a CRH antagonist. This suggests that the new non-peptide CRH1 receptor antagonists that enter the brain might provide an effective treatment for the behaviour abnormalities in the offspring arising as a result of gestational stress.