Abstract: AIM: To observe whether clozapine can alter the synaptic transmission and extracellular neurotransmitters release in the hippocampus of rabbits. METHODS: The stimulating microelectrodes were inserted into the perforant path of hippocampus in 15 rabbits, while the recording microelectrodes and guide cannulas were inserted into homolateral dentate gyrus of the rabbits. After a 10-day recovery period, they were divided into three groups randomly (n=5): contral(C) group, tetanic stimulation (T) group and without tetanic stimulation (N) group. There were 3 sessions (60 mins/session) in the total 180 mins. Every rabbit was given single stimuli at a fixed intensity(monopolar square pulse of 0.2 ms duration, 200-300 μA,30-second stimulus intervals) in dentate gyrus. T and N were intraperitoneally injected with clozapine resolution(20 mg/kg) and C were intraperitoneally injected with blank solvent after 60 min, while C and T were given a titanic stimulation after 120 min. The synaptic responses in dentate gyrus were recorded every 2 min, and the microdialysis samples were collected to examine the extracellular DA and 5-HT levels every 5 min. RESULTS: The response in dentate gyrus: there was clozapine-induced potentiation in group T and N in session 2(P＝0.004), and there was LTP in group T and C in session 3(P＝0.02). The extracellular DA and 5-HT levels: DA levels were increased significantly in group T in session 2 and 3 when compared with session 1(ther was not responding change of DA levels in session 3)(P＜0.01), DA levels were increased significantly in group N after clozapine administration(P＜0.01), while DA levels in group C and the levels of 5-HT in 3 groups were not changed(P＞0.05). CONCLUSION: Clozapine almost affect the excitatory synaptic response and extracellular DA levels in hippocampus simultaneously.

Key words: Clozapine-induced potentiation, Dopamine, Serotonin, Long-term potentiation