2015年7月
Prefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits
ELIFE
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- 巻
- 4
- 号
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.7554/eLife.08274
- 出版者・発行元
- ELIFE SCIENCES PUBLICATIONS LTD
Prevention of relapses is a major challenge in treating anxiety disorders. Fear reinstatement can cause relapse in spite of successful fear reduction through extinction-based exposure therapy. By utilising a contextual fear-conditioning task in mice, we found that reinstatement was accompanied by decreased c-Fos expression in the infralimbic cortex (IL) with reduction of synaptic input and enhanced c-Fos expression in the medial subdivision of the central nucleus of the amygdala (CeM). Moreover, we found that IL dopamine plays a key role in reinstatement. A reinstatement-inducing reminder shock induced c-Fos expression in the IL-projecting dopaminergic neurons in the ventral tegmental area, and the blocking of IL D1 signalling prevented reduction of synaptic input, CeM c-Fos expression, and fear reinstatement. These findings demonstrate that a dopamine-dependent inactivation of extinction circuits underlies fear reinstatement and may explain the comorbidity of substance use disorders and anxiety disorders.
- リンク情報
- ID情報
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- DOI : 10.7554/eLife.08274
- ISSN : 2050-084X
- PubMed ID : 26226637
- Web of Science ID : WOS:000373881000001