The hypothalamic neural mechanisms that are involved in the facilitatory effects of the amygdala (AMG) on the hypothalamo-pituitary-adrenocortical (HPA) axis have been investigated in rats. Stimulation of the central AMG nucleus caused a depletion of hypothalamic CRF-41, presumably due to its release into the portal circulation, and a subsequent rise in plasma ACTH and corticosterone (CS) levels, These effects were inhibited in rats in which hypothalamic norepinephrine (NE) or serotonin (5-HT) was depleted by catecholamine or serotonin neurotoxins, respectively. Furthermore, the administration of prazosin, an alpha 1, but not of atenolol, which is a beta-blocker, as well as administration of the 5-HT2 blocker ketanserin inhibited the ACTH and CS responses to AMG stimulation. These results indicate that the facilitatory effects of the AMG on the HPA axis are mediated by hypothalamic NE via alpha 1 receptors and by 5-HT via 5-HT2 receptors, as well as by CRF-41 in the paraventricular nucleus. (C) 1998 Elsevier Science Inc.