Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient sandy mice: An in vivo microdialysis study

Taku Nagai, Yuko Kitahara, Anna Shiraki, Takao Hikita, Shinichiro Taya, Kozo Kaibuchi, Kiyofumi Yamada

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Dystrobrevin binding protein-1 gene (DTNBP1), which encodes dysbindin protein, has been identified as a schizophrenia susceptibility gene. Dysbindin has been shown to contribute to the regulation of exocytosis and formation of synaptic vesicles. Although hypofrontality in schizophrenia underlies its pathophysiology, the molecular function of dysbindin in synaptic neurotransmission remains unclear. In the present study, we investigated depolarization-evoked dopamine (DA) and serotonin (5-HT) release in the prefrontal cortex (PFC) of sandy (sdy) mice, which have a deletion mutation in the gene encoding DTNBP1. In vivo microdialysis analysis revealed that extracellular DA levels in the PFC of wild-type mice were increased by 60 mM KCl stimulation, and the KCl-evoked DA release was significantly decreased in sdy mice compared with wild-type mice. Extracellular 5-HT levels in the PFC of wild-type mice were also increased by 60 mM KCl stimulation. The KCl-evoked 5-HT release did not differ between wild-type and sdy mice. There was no difference in basal levels of DA and 5-HT before the stimulation between two groups. Behavioral sensitization after repeated methamphetamine (METH) treatment was significantly reduced in sdy mice compared with wild-type mice whereas no difference was observed in METH-induced hyperlocomotion between two groups. These results suggest that dysbindin may have a role in the regulation of depolarization-evoked DA release in the PFC and in the development of behavioral sensitization induced by repeated METH treatment.

Original languageEnglish
Pages (from-to)134-138
Number of pages5
JournalNeuroscience Letters
Volume470
Issue number2
DOIs
Publication statusPublished - 12-02-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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