| Project/Area Number |
09671012
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Nihon University |
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Principal Investigator |
KASAMO Kimihiro Nihon University, Assistant, 医学部, 講師 (90204370)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Takuya Nihon University, Professor, 医学部, 教授 (40014203)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | excitatory amino acid / contextual fear / serotonin1A receptor / hippocampal CA1 pyramidal neuron / unit recording / kainate receptor / electrophysiology / behavioral pharmacology / ラット / 恐怖条件付けストレス / セロトニン / 不安 / 海馬 / ベンゾジアゼピン / 微小イオン注入法 / 錐体細胞 / アセチルコリン |
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| Research Abstract |
Conditioned-fear induced freezing behavior in an animal model of fear or anxiety generated by memory and cognition. Previous brain lesioning studies have shown that the hippocampus plays important role roles in the expression of the freezing behavior. In these 3 years, we have shown the following issues in animal studies using male adult Wistar rats :
・ It is well known that 5-HT1A agonists, SSRIs and benzodiazepines have anxiolytic properties. Among these anxiolytic drugs, 5-HT1A agonist buspirone, and SSRIs sertraline and fluvoxamine suppress the spontaneous firing activity of dorsal hippocampus CA1 pyramidal neurons whereas the effect of a benzodiazepine derivative alprazolam varied across the tested neurons.
・ Using urethane anesthetized rats, we examined effects of buspirone and alprazolam on the firing activity of the CA1 pyramidal neurons induced by microiontophoretic applications of acetylcholine (Ach), NMDA, quisqualate or kainate. Buspirone inhibited the firing activities induced by any of these compounds whereas alprazolam suppressed the kainate-induced firing activity only. These observations indicated that stimulation of kainate receptors in the rat brain might play a crucial role in generating the conditioned fear.
・ Indeed, an antagonist for AMPA/kainate receptor CNQX inhibited the conditioned fear stress-induced freezing behavior in our behavioral experiments.
・ During such freezing behavior, the spontaneous firing activity of dorsal hippocampus CA1pyramidal neurons was decreased by the facilitated stimulations of postsynapitc 5-HT1A receptors that would have resulted from an increase in extracellular 5-HT.
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