This study examined the central effects of rat prepro-TRH 178-199, a peptide with corticotropin release inhibiting activity at the pituitary, on the Porsolt forced swim test (FST) of depressive behavior in rats. Subacute intracerebroventricular administration of prepro-TRH 178-199 dose-responsively reduced floating and increased active behaviors in the FST. Chronic administration of 6 microg/kg prepro-TRH 178-199 decreased floating more than subacute treatment, but there were no significant differences between chronic and subacute treatment effects on active behavior. Biological activity of this peptide resides in the C-terminal fragment as prepro-TRH 178-199 and prepro-TRH 191-199 were equally potent in the FST. These data suggest that endogenous prepro-TRH 178-199 with its antidepressant-like activity might contribute to the etiology or manifestation of depressive behavior.