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オシブチ ヒデヒロ
OSHIBUCHI Hidehiro
押淵 英弘 所属 医学部 医学科（東京女子医科大学病院） 職種 准教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Dopamine dynamics during emotional cognitive processing: Implications of the specific actions of clozapine compared with haloperidol. |
| 掲載誌名 | 正式名：European journal of pharmacology 略 称：Eur J Pharmacol ISSNコード：(1879-0712)0014-2999(Linking) |
| 掲載区分 | 国外 |
| 巻・号・頁 | 781,pp.148-56 |
| 著者・共著者 | Kawano Masahiko, Oshibuchi Hidehiro, Kawano Takaaki, Muraoka Hiroyuki, Tsutsumi Takahiro, Yamada Makiko, Inada Ken, Ishigooka Jun |
| 担当区分 | 2nd著者 |
| 発行年月 | 2016/06 |
| 概要 | Clozapine has improved efficacy relative to typical antipsychotics in schizophrenia treatment, particularly regarding emotional symptoms. However, the mechanisms underlying its therapeutic benefits remain unclear. Using a methamphetamine-sensitised rat model, we measured changes in dopamine levels in the amygdalae in response to a fear-conditioned cue, serving as a biochemical marker of emotional cognitive processing disruption in psychosis, for analysing the biochemical mechanisms associated with the clinical benefits of clozapine. We also compared how clozapine and haloperidol affected basal dopamine levels and phasic dopamine release in response to the fear-conditioned cue. Extracellular dopamine was collected from the amygdalae of freely moving rats via microdialysis and was analysed by high-performance liquid chromatography. Clozapine or haloperidol was injected during microdialysis, followed by exposure to the fear-conditioned cue. We analysed the ratio of change in dopamine levels from baseline. Haloperidol treatment increased the baseline dopamine levels in both non-sensitised and sensitised rats. Conversely, clozapine only increased the basal dopamine levels in the non-sensitised rats, but not in the sensitised rats. Although both antipsychotics attenuated phasic dopamine release in both the non-sensitised and sensitised rats, the attenuation extent was greater for clozapine than for haloperidol under both dopaminergic conditions. Our findings indicate that stabilized dopamine release in the amygdalae is a common therapeutic mechanism of antipsychotic action during emotional processing. However, the specific dopaminergic state-dependent action of clozapine on both basal dopamine levels and stress-induced dopamine release may be the underlying mechanism for its superior clinical effect on emotional cognitive processing in patients with schizophrenia. |
| DOI | 10.1016/j.ejphar.2016.04.013 |
| PMID | 27085900 |