Abstract: AIM: To study effects of clausenamide on synaptic transmission of the hippocampal dentate gyrus in freely-moving rats. METHODS: With extracellular recording technique, the effects of (-)-clausenamide and (+)-clausenamide on synaptic transmission of the dentate gyrus in freely-moving rats were observed. RESULTS: Long-term potentiation (LTP) induced by high-frequency stimulation (HFS, 50 pulses at 200 Hz) lasted for at least 5 days. When (-)-clausenamide (8　mg.kg^-1, po) was administered once daily for 7 consecutive days, amplitude of population spikes (PS) began to increase from the 3rd day and almost reached its maximum on the 5th day. There was no significant decrease even on the 5th day after drug withdrawal, but the stimulus threshold for inducing PS changed contrarily to the PS amplitude. (+)-clausenamide at the same dose as (-)-clausenamide did not significantly affect the PS amplitude and the stimulus threshold for inducing PS. CONCLUSION: These results suggest that orally-administered clausenamide can enter the brain tissue to effectively affect synaptic transmission and the effects of clausenamide on the synaptic transmission in the dentate gyrus of freely-moving rats depend on its chirality.