The role of neuropeptide Y (NPY) in the mediation of orexin-induced hypotha
lamic-pituitary-adrenal (HPA) activation was investigated in the rat. The H
PA system was stimulated by intracerebroventricular (i.c.v.) administration
of orexin-A or orexin-B (140 or 280 pmol, respectively) and the plasma con
centration of corticosterone was used as an index of the degree of activati
on. i.c.v. pretreatment with NPY antagonist or NPY antiserum (30 min or 24
h before orexin administration, respectively) inhibited the orexin-induced
corticosterone release. The inhibitory actions of the antagonist and the an
tiserum were revealed by the dose-response curve; the highest concentration
s practically abolished the HPA activation evoked by the orexins. These dat
a suggest that the HPA system-stimulating effect of the orexins may be medi
ated by NPY.