Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits.
We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine's clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path-dentate gyrus pathway.
Kubota
Takashi
T
Department of Neuropsychiatry, Kanazawa Medical University, Uchinada-Machi, Kahoku-gun, Ishikawa 920-0293, Japan. t-kubota@kanazawa-med.ac.jp
Jibiki
Itsuki
I
Ishikawa
Akira
A
Kawamura
Tomomi
T
Kurokawa
Sonoko
S
Wang
Man
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009473:Neuronal Plasticity / Q000187:drug effects*; D019580:Perforant Pathway / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation
D014150:Antipsychotic Agents; D012701:Serotonin; D003024:Clozapine; D004298:Dopamine