The present study was undertaken to examine the relationships among the levels of nitric oxide (NO), monoamines, and blood glucose in the diabetic hippocampus. The levels of NO and monoamines (serotonin, 5-hydroxytryptamine [5-HT] and dopamine [DA]) were simultaneously measured in several experiments, using in vivo microdialysis techniques. We used both experimentally and spontaneously diabetic rats as the diabetic animal model, and compared the findings with those obtained from non-diabetic rats. The effects of the changed level of blood glucose due to insulin administration on the levels of NO, 5-HT, and DA were assessed. Total NO metabolite levels (NOx) were calculated as the sum of nitrite (NO2-) and nitrate (NO3-) levels. The results in the present study showed that: (1) the plasma levels of NOx in both diabetic rats were low compared to those in control rats, (2) the hippocampal NOx levels in both diabetic rats were almost the same as those in control rats, while the levels of 5-HT and DA were low in the diabetics, and (3) a sudden decrease in the plasma glucose level due to insulin administration reduced the NOx level as well as enhanced the 5-HT level in the diabetic hippocampus, a finding consistent with the results of 7 days administration of insulin. Taken together, these findings suggest that changes in the plasma glucose level cause, at least in part, the changes in the levels of NOx and monoamines in the diabetic brain. (C) 2003 Elsevier Science Ltd. All rights reserved.