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- Title
Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits.
- Authors
Kubota, Takashi; Jibiki, Itsuki; Ishikawa, Akira; Kawamura, Tomomi; Kurokawa, Sonoko; Man 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 present study implies that such phenomena occur also in the perforant path-dentate gyrus pathway.
- Subjects
DOPAMINE; CLOZAPINE; DENTATE gyrus; HIPPOCAMPUS (Brain); LABORATORY rabbits; COGNITION disorders
- Publication
Canadian Journal of Physiology & Pharmacology, 2008, Vol 86, Issue 5, p249
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/Y08-036