Effect of Stress Exposure on the Activation Pattern of Enkephalin-Containing Perikarya in the Rat Ventral Medulla

Integration of the hypothalamo-pituitary-adrenal stress response occurs by way of interactions between stress-sensitive brain circuitry and neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN). Stressors involving an immediate physiologic threat ('systemic' stressors) are relayed directly to the PVN, probably via brainstem catecholaminergic projections. By contrast, stressors requiring interpretation by higher brain structures ('processive' stressors) appear to be channeled through limbic forebrain circuits. Forebrain limbic sites connect with the PVN via interactions with GABA-containing neurons in the bed nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final elaboration of processive stress responses is likely to involve modulation of PVN GABAergic tone. The functional and neuroanatomical data obtained suggest that disease processes involving inappropriate stress control involve dysfunction of processive stress pathways.

Experiments using two retrogradely transported fluorescent dyes (bisbenzimide-true blue, and Evans blue-granular blue) were performed in order to determine whether the same or different populations of neurons of the paraventricular nucleus of the hypothalamus (PVH) project to the pituitary gland, dorsal vagal complex, and spinal cord in the rat. The results suggest that cells projecting to the pituitary gland are concentrated in the magnocellular core of the nucleus, while the descending connections arise primarily from the surrounding parvocellular division. The occurrence of neurons double-labeled with both dyes further indicate that at lease 10-15% of the labeled cells in the parvocellular division send divergent axon collaterals to the dorsal vagal complex and to the spinal cord. Cell counts suggest that at least 1,500 cells in the PVH project to the medulla and/or spinal cord. These results, combined with a cytoarchitectonic analysis, show that the PVH consists of eight distinct subdivisions, three magnocellular and five parvocellular. The lateral hypothalamic area and zona incerta also contain a large number of cells projecting to the dorsomedial medulla and spinal cord; approximately 15% of such cells are the double-labeled following injections of separate tracers into these two regions of the same animal.