Intracerebroventricular (i.c.v.) administration of the octadecaneuropeptide (diazepam-binding inhibitor [33-50]; ODN) exerts a potent anorexigenic effect in the rat. We studied the effect of ODN on three neuropeptides involved in feeding behaviour: the orexigenic peptide neuropeptide Y (NPY) and two anorexigenic peptides, corticotropin-releasing hormone (CRH) and the pro-opiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone. The effect of i.c.v. administration of ODN (0.1 microg/kg and 1 microg/kg) on mRNA expression of the peptides in male rat hypothalamus was evaluated by semiquantitative in situ hybridization. In the arcuate nucleus, NPY-expressing neurones were mostly found in the inner zone in close proximity of the third ventricle. ODN at the dose of 0.1 microg/kg induced a significant decrease of 17.4% in NPY mRNA expression, while the depressing effect was more marked (31.4%) with the highest dose of ODN (1 microg/kg). POMC-expressing neurones were more laterally located in the arcuate nucleus. Administration of ODN at 0.1 microg/kg and 1 microg/kg doses induced increases of 33.5% and 27.4% in POMC mRNA expression, respectively. Labelling obtained with the CRH cRNA probe was essentially distributed throughout the medial parvocellular area of the hypothalamic paraventricular nucleus. ODN, at doses of 0.1 and 1 microg/kg, resulted in 17.8% and 32.8% decreases in CRH mRNA expression, respectively. The present data suggest that ODN might exert its anorexigenic effect by increasing mRNA expression of POMC and decreasing mRNA expression of NPY in the arcuate nucleus.