@article{ref1,
title="Prefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits",
journal="Elife",
year="2015",
author="Hitora-Imamura, Natsuko and Miura, Yuki and Teshirogi, Chie and Ikegaya, Yuji and Matsuki, Norio and Nomura, Hiroshi",
volume="4",
number="ePub",
pages="ePub-ePub",
abstract="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.<p /><p>Language: en</p>",
language="en",
issn="2050-084X",
doi="10.7554/eLife.08274",
url="http://dx.doi.org/10.7554/eLife.08274"
}