Stress-induced alterations in locus coeruleus gene expression during ontogeny

Brainstem noradrenergic neurons, particularly the locus-coeruleus (LC), play a pivotal role in modulating the central stress response and have been implicated in regulating the hypothalamic-pituitary-adrenal (HPA) axis. In adult rats, acute stress causes an increase in LC firing and tyrosine hydroxylase (TH) gene expression. While the role of the LC-norepinephrine (LC-NE) system in the adult stress response has been well characterized, there is limited evidence for its participation during development. Previous studies described the neonatal HPA axis as hyporeactive because of stimulus-selective pituitary activation. However, maternal deprivation does reinstate stress-induced endocrine activity and can amplify the neural stress response. Considering that LC neurons can modulate neuroendocrine activity, we hypothesized that the LC-NE system would be stress-responsive during development. Because maternal deprivation (DEP) can alter the central stress response, we examined the LC-NE stress response in both DEP and non-deprived (NDEP) pups. Following an isotonic saline injection (stressor) the time course of TH, c-fos and glucocorticoid receptor (GR) mRNA was examined. Stress-induced TH mRNA was increased in DEP pups at postnatal day (pnd) 12 and in both NDEP and DEP pups at pnd 18. At 15, 30 and 240 min c-fos mRNA was markedly increased in all groups examined. GR mRNA was not altered at pnd 12; however, at pnd 18 NDEP pups showed reduced GR mRNA expression. These data indicate that during ontogeny the LC-NE system is stress-responsive to an acute mild challenge. Activation of LC-NE neurons suggests that this system may participate in modulating the neuroendocrine stress response during development.