Citation

Hitora-Imamura N, Miura Y, Teshirogi C, Ikegaya Y, Matsuki N, Nomura H. Elife 2015; 4(ePub): ePub.

Affiliation

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States.

Copyright

(Copyright © 2015, dLife Sciences Plublications, Ltd)

DOI

10.7554/eLife.08274

PMID

26226637

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.

Language: en