Neurotensin (NT), a peptide present both in the brain and in the gastrointestinal tract, has potent anorexigenic effects when centrally injected in rats and is secreted after fat ingestion. High fat diets are often associated with increased energy intake. The aim of this study was therefore to evaluate the role of neurotensin in the feeding behaviour of rats fed on a high fat (HF) diet. Adult Long-Evans rats were fed for two weeks either a control (C) well-balanced diet (n = 10) or a fat-rich diet containing about two-thirds of its energy as fat (margarine and peanut oil; n = 10). Neurotensin was measured by a specific radioimmunoassay in the plasma and in several microdissected brain nuclei involved in the regulation of feeding behaviour. Ingestion of the HF diet induced an increased body weight gain (47.6 +/- 7.7 g (HF) vs. 37.6 +/- 9.3 g (C); P less than 0.05) and an increased energy intake (+ 7.2%; P less than 0.05). Plasma fasting NT concentrations were not affected by the HF diet. In the hypothalamus, significant decreases in NT concentrations were measured in the HF rats in two nuclei important in the regulation of food intake, i.e. the paraventricular nucleus (1.72 +/- 0.16 (HF) vs. 2.27 +/- 0.15 (C) ng/mg protein; P less than 0.05) and the lateral hypothalamus (1.87 +/- 0.16 (HF) vs. 2.37 +/- 0.19 (C) ng/mg protein; P less than 0.05). On the other hand, no variations were measured in the ventral tegmental area, an important site for the metabolism and regulatory action of neurotensin and in other hypothalamic nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)