INHIBITION OF STRESS-INDUCED NEUROENDOCRINE AND BEHAVIORAL-RESPONSES IN THE RAT BY PREPRO-THYROTROPIN-RELEASING HORMONE-178-199

A corticotropin release-inhibiting factor (CRIF) in brain has been pos tulated for several decades, based on increased plasma levels of ACTH and corticosterone after hypothalamic-pituitary disconnection. Recent in vitro studies indicate that prepro-TRH178-199 may function as an en dogenous CRIF, prompting us to examine stress-related neuroendocrine a nd behavioral responses after in vivo administration to the adult male rat. Animals that were administered prepro-TRH178-199 intravenously 5 min before restraint stress exhibited a significant attenuation of st ress-induced elevations of ACTH, corticosterone, and prolactin, as com pared with controls infused with vehicle, whereas thyroid-stimulating hormone (TSH) secretion was not changed. In behavioral studies of stre ss responsiveness, either the vehicle or prepro-TRH178-199 was adminis tered intracerebroventricularly (ICV) 5 min before testing. In the ope n field, prepro-TRH178-199 significantly increased grooming, locomotor activity, rearing, and sniffing behaviors. In the light/dark box, it significantly increased the time animals spent in the light compartmen t and increased the number of crossings between the light/dark compart ments. In the plus maze, the peptide significantly increased the amoun t of time animals spent in the open arms. The same dose of peptide, ad ministered ICV, had no effect on peripheral hormone release in respons e to restraint stress. Overall, these results support a role for prepr o-TRH178-199 in the inhibition of the neuroendocrine responses to stre ss at the level of the pituitary and indicate that it has central modu latory influences over stress-related behaviors.