Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits

Canadian Journal of Physiology and Pharmacology
Takashi KubotaMan Wang

Abstract

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 presen...Continue Reading

References

Jan 1, 1991·Schizophrenia Bulletin·A SaffermanB Kinon
Jan 16, 1998·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·J Arnt, T Skarsfeldt

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Citations

May 14, 2014·Progress in Neuro-psychopharmacology & Biological Psychiatry·Rae PriceTarek K Rajji

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