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A corticotropin release-inhibiting factor (CRIF) in brain has been postulated 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 endogenous CRIF, prompting us to examine stress-related neuroendocrine and 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 stress-induced elevations of ACTH, corticosterone, and prolactin, as compared with controls infused with vehicle, whereas thyroid-stimulating hormone (TSH) secretion was not changed. In behavioral studies of stress responsiveness, either the vehicle or prepro-TRH178–199 was administered intracerebroventricularly (ICV) 5 min before testing. In the open 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 compartment and increased the number of crossings between the light/dark compartments. In the plus maze, the peptide significantly increased the amount of time animals spent in the open arms. The same dose of peptide, administered ICV, had no effect on peripheral hormone release in response to restraint stress. Overall, these results support a role for prepro-TRH178–199 in the inhibition of the neuroendocrine responses to stress at the level of the pituitary and indicate that it has central modulatory influences over stress-related behaviors.

Inhibition of Stress-Induced Neuroendocrine and Behavioral Responses in the Rat by Prepro-Thyrotropin-Releasing Hormone 178–199