AIM: To investigate the mechanisms of l-clausenamide-induced long-term potentiation (LTP) in the dentate gyms of anesthetized rats. METHODS: Extracellular recording technique was used to record the population spike (PS) in the dentate gyrus of anesthetized rats. RESULTS: Icy injection of naloxone I nmol, affecting neither the basal PS amplitude nor the LTP induced Ly tetanus, reduced the l-clausenamide-potentiated LTP only when it was administrated prior to clausenamide. Naloxone I nmol (icv), administrated 10 min before l-clausenamide, reduced the PS amplitude at 20 min, 55 min, and 90 min after icy injection of l-clausenamide 4 nmol from 138 % +/- 10 %, 170 % +/- 10 %, and 169 % +/- 12 % to 111 % +/- 7%, 124 % +/- 14 %, and 123 % +/- 11, respectively. All P < 0.01 (Ir = 8). The same dose of naloxone (icv), delivered 10 min after l-clausenamide, did not affect the l-clausenamide-induced potentiation. CONCLUSION: The activation of opioid receptors contributes to the induction of l-clausenamide-induced LTP of synaptic transmission in dentate gyrus of anesthetized rats.