BACKGREOUND: Since it has been reported that ketamine, an intravenous anesthetic, is a non-competitive antagonist of N-methyl-D-aspartic acid (NMDA) receptors, a large number of experimental data on the several mechanism of this process have been accumulated. But the mechanism about the effect of ketamine on neurotransmitter release in central nervous system has not been clearly elucidated yet. Therefore the present study was undertaken to investigate the effects of ketamine and thiopental sodium on hippocampal norepinephrine (NE) release, and also to examine the relationship between ketamine and NMDA receptor mechanisms in the rat hippocampus. METHODS: Slices from rat hippocampus were equilibrated with [3H]norepinephrine ([3H]NE) and the release of labelled products was evoked by electrical stimulation (3 Hz, 5 V/cm, 2 ms, rectangular pulses, 2 min), and the influence of various agents on the evoked tritium-outflow and the basal rate of release were investigated. RESULTS: In rat hippocampal slices, ketamine (1~30 micrometer) and thiopental sodium (1~30 micrometer) did not affect the evoked NE release and the basal release in the normal and Mg2 free medium. NMDA (3~100 micrometer) did not alter the NE release in the normal medium, but NMDA (1~30 micrometer) increased the basal rate of NE release in the Mg2 free medium. The increasing effects of NMDA on basal release were completely abolished by ketamine treatment in a concentration dependent manner. But, thiopental sodium did not affect the NMDA effect. CONCLUSIONS: These results suggest that increment of the basal rate of NE release is mediated by NMDA receptor in the rat hippocampus and ketamine completely block this effect, but thiopental sodium is not involved in these process.