2000 Fiscal Year Final Research Report Summary
Study on the role of emotional stress for the pathogenesis of psychiatric disorders. -To clarify the relationship between emotional stress and central monoaminergic/peptidergic neural systems using animal models-
| Project/Area Number |
09470205
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KOYAMA Tsukasa Hokkaido Univ.Grad.School of Medicine, Prof., 大学院・医学研究科, 教授 (10113557)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Takeshi Hokkaido University, Medical Hospital, Lec., 医学部・附属病院, 講師 (70250438)
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| Project Period (FY) |
1997 – 2000
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| Keywords | Anxiety / Serotonin / SSRI / Monoamine oxidase inhibitor / amygdala / Dopamine / mRNA / Lithium |
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| Research Abstract |
The purpose of this study is to clarify the effect of conditioned fear stress on central monoaminergic and peptidergic systems using in vivo microdialysis, radioimmunoassay, in situ hybridization, and Northern Blot in discrete brain regions and to examine functional localization of neural systems.
1) Selective serotonin reuptake inhibitors (SSRIs) reduced conditioned freezing, an index of anxiety, and these anxiolytic effects were enhanced by subchronic lithium pretreatment at the therapeutic plasma lithium levels.
The anxiolytic effects of serotonin1A agonists were also enhanced by subchronic lithium pretreatment. In vivo microdialysis studies showed that subchronic lithium treatment increased basal levels of extracellular serotonin and induced additive effects on SSRI-induced increases in extracellular serotonin.
2) The anxiolytic effects of monoamine oxidase inhibitors (MAOIs) were tested in the conditioned fear model. MAO-A inhibitors or MAO-B inhibitors did not induce anxiolytic effects, but non-selective MAOIs and the combination of MAO-A and MAO-B inhibitors were anxiolytic. In vivo microdialysis studies showed that the combination of MAO-A and MAO-B inhibitors induced more increases in extracellular serotonin than either inhibitor alone did.
3) Lithium and SSRI treatment increased the level of dopamine2 receptor mRNA and the transcription rate of the dopamine2 receptor gene in the rat striatum.
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