PURPOSE: Hippocampus contains interneurons where neuropeptide Y is located, but the connectivity of these has not been well studied. Neuropeptide Y may influence the serotonergic nervous system through the interneurons. Serotonergic nerve fibers pass through nearly all areas of the hippocampus. We investigate the effects of Neuropeptide Y on serotonin release from rat hippocampal slices for the better understanding of the effects of neuropeptide Y at the hippocampus. MATERIALS AND METHODS: The hippocampus was obtained from the male rat brain and sliced. The slices were incubated in a buffer containing 0.1 mM [3H]5-hydroxytryptamine (5-HT) for uptake. The release of 5-HT into the buffer during each 10 min period was measured and the radioactivities in each buffer and the tissue were counted using liquid scintillation counter and the results were expressed as a percentage of the total activity. After 50 min from the initiation, neuropeptide Y were administered at 6th and 7th 10 min period, respectively. The changes of 5-HT release were expressed as percent values compared to the 5th 10 min period. RESULTS: A steady release of 5-HT was observed up to 100 min after the rapid release during the first 40 min. The 5-HT release during 10 and 20 min of neuropeptide Y (10 6 M) treatment showed no significant change. CONCLUSIONS: The release of 5-HT was not changed by neuropeptide Y and this results suggest that neuropeptide Y does not influence the serotonergic nervous system through the interneurons.