Stressor-specific activation of the hypothalamic-pituitary-adrenocortical axis

New information has accrued from in vivo microdialysis studies about stress -related changes in norepinephrine concentrations in extracellular fluid of the paraventricular nucleus (PVN) and the activation of the hypothalamic-p ituitary-adrenocortical (HPA) axis. Our data on the effects of lower brains tem hemisections show that paraventricular noradrenergic terminals are deri ved mainly from medullary A1 and A2 catecholaminergic cells. The activation of these cells contributes importantly to stress-induced noradrenergic act ivation in the paraventricular nucleus of conscious animals. The results fr om brainstem hemisection experiments also indicate that baseline levels and immobilization-induced increments in corticotropin-releasing hormone (CRH) mRNA expression in the PVN depend on ipsilaterally ascending medullary tra ct. Thus, the prevalent: concept that stress-induced noradrenergic activati on of the HPA axis depends mainly on activation of locus ceruleus noradrene rgic neurons requires re-evaluation. Our new stress concepts favor stressor -specific activation of the HPA axis. The present data also suggest the exi stence of stressor-specific central pathways that differentially participat e in the regulation of sympathoneuronal and adrenomedullary outflows as wel l as of the activity of the HPA axis. Furthermore, the results are inconsis tent with a founding tenet of Selye's stress theory, the doctrine of nonspe cificity, which defines stress as the nonspecific response of the body to a ny demand, We expect that future studies in this area will focus on further examination of the notion of stressor-specific patterns of central neurotr ansmitter release and elucidate the genetic bases of these patterns.