To reveal the role of serotonergic neurons in the regulation of feeding, the levels of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin, in the striatum and the hypothalamus were continuously monitored by an in vivo microdialysis technique. Intake of 20% casein diet did not induce significant changes in the 5-HIAA level in these regions. When rats were fed on 5% casein diet (83.5% carbohydrate diet) for 2 h, the level of 5-HIAA in the striatum gradually increased and reached a maximum (226 +/- 44% of basal level, M +/- SEM, n = 7) at 4 h after stopping the diet. In the medial hypothalamus, its level also increased to 183 +/- 19% (n = 10) at 2 h after starting the diet. On the other hand, a 60% casein diet increased the level of 5-HIAA in the lateral hypothalamus to 138 +/- 19% (n = 10) at 2 h after starting the diet. The intravenous infusion of each of these nutrients, glucose, amino acid mixture or lipid, produced more rapid elevation of the 5-HIAA level than oral intake of the diets. When rats were infused with glucose, its level in the striatum continued to be elevated. In the medial hypothalamus, glucose infusion increased 5-HIAA to the maximum (189 +/- 38%, n = 7) at 4 h after starting infusion. In contrast, serotonergic neurons in the lateral hypothalamus seemed to respond only to infusion of the amino acid mixture, and the level of 5-HIAA reached 163 +/- 14% (n = 5) of the basal level at 1 h after starting the infusion. These results suggest that rapid elevation of glucose or amino acids may independently stimulate serotonin metabolism in these brain areas, participating in the feedback regulation of nutrient intake.