DIFFERENTIAL DEVELOPMENT OF THE STRESS-RESPONSE IN CONGENITAL LEARNED HELPLESSNESS

Early in the development of the hypothalamic-pituitary-adrenal (HPA) axis, the rat undergoes a stress hyporesponsive period of blunted responses to several stressors including cold exposure (CE) and maternal deprivation (MD). We examined the development of the axis by monitoring adrenocorticotropin hormone (ACTH) plasma levels in an animal model of depression and/or anxiety characterized by learned helpless (LH) behavior and a dysfunctional HPA axis in adult life. On postnatal day 7 there was no significant difference in basal plasma ACTH levels between congenital (cLH) and controls, but cLH animals showed a blunted response to CE (P<0.001). By postnatal day 14 there was a dramatic increase in ACTH response to CE (P<0.005). On postnatal day 21 baseline ACTH and response to CE were again significantly suppressed in cLH rats. Stress responsiveness to MD was present in all groups and was insignificantly different for all ages of development between groups. These findings suggest that rats with congenital learned helplessness undergo a differential response in the development of the HPA axis in that the axis was hypersensitive at postnatal day 14 and became hyporesponsive beyond day 14, and this may, in part, account for the dysfunctional stress response observed during adulthood.