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In pentobarbital-anesthetized rats, RX77368 (50 ng) ic induced a significant bipeak increase in serum total ghrelin levels from the basal of 8.7 \u00b1 1.7 ng\/ml to 13.4 \u00b1 2.4 ng\/ml at 30 min and 14.5 \u00b1 2.0 ng\/ml at 90 min, which was prevented by either bilateral vagotomy (\u221260 min) or atropine pretreatment (2 mg\/kg, \u221230 min) but magnified by bilateral adrenalectomy (\u221260 min). TRH analog ic-induced food intake in freely fed rats was abolished by either peripheral atropine or ghrelin receptor antagonist (d-Lys-3)-GHRP-6 (10 \u03bcmol\/kg) or ic Y1 receptor antagonist 122PU91 (10 nmol\/5 \u03bcl). Brain stem TRH mRNA and TRH receptor 1 mRNA increased by 57\u201358 and 33\u201335% in 24- and 48-h fasted rats and returned to the fed levels after a 3-h refeeding. Natural food intake in overnight fasted rats was significantly reduced by ic TRH antibody, ic Y1 antagonist, and peripheral atropine. 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