The projection fields of corticotropin-releasing factor (CRF)-containing perikarya in the rat central nervous system were studied using a combination of electrolytic lesions, microdissection and radioimmunoassay. The effects of bilateral electrolytic lesions of the central nucleus of the amygdala (Ce) or the paraventricular nucleus (PVN) of the hypothalamus were measured by a sensitive and specific radioimmunoassay. Following lesions of the Ce, CRF concentrations in the locus ceruleus (LC) were significantly decreased. Following lesions of the PVN, CRF concentrations in the median eminence were markedly decreased (> 85%), with smaller but consistent reductions of CRF in the hippocampus as well. In contrast to the Ce lesions, PVN lesions resulted in increases in CRF concentrations in the LC. These results further confirm the projection of CRF-containing cells from the PVN to the median eminence, provide evidence for a PVN-hippocampal CRF pathway, and suggest that the PVN modulates CRF neurons innervating the LC. Moreover, the existence of a CRF-containing pathway from the Ce to the LC appears likely, and such a circuit may play a role in the behavioral and physiological responses to stress.

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