[Reduction and sensitization of CRH neuron in rat hypothalamic and extrahypothalamic regions after chronic variable...

The hyperactivity of corticotropin-releasing hormone (CRH) neurons of the hypothalamic and/or extrahypothalamic regions is believed to contribute to the pathophysiology of major depression in an experimental animal chronically exposed to stress. In the present study, we examined the effects of chronic variable stress (CVS) and novel stress (footshock) on the CRH immunoreactivity in the hypothalamic paraventricular nucleus (PVN) and subdivision of PVN, and the extrahypothalamic bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA). We observed a significant reduction in CRH levels in the whole PVN, lateral parvocellular part of PVN, BNST and CeA 24 hours after the last stressor of CVS for 13 days. A novel stressor after CVS caused a marked increase in CRH levels in these four regions, followed a further reduction observed 24 hours later. Since the CVS-induced modulation of CRH levels are consistent with an alteration of tyrosine hydroxylase levels in the locus coeruleus, CRH-norepinephrine (NE) interaction in the terminal projection of forebrain NE systems, PVN, BNST and CeA where NE stimulates CRII release, might contribute to the bi-directional change in CRH. The CVS-induced bi-directional changes in CRH of PVN, BNST and CeA might play a role in the formation of the pathophysiology of major depressive disorders.