Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Published: July 2015
AI Article Synopsis
Article 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.
Exposure therapy is an efficient treatment for pathological anxiety, yet its underlying mechanisms are not fully understood. Prediction error models suggest that optimizing the violation of threat-related expectancies improves treatment outcomes, however, causal evidence is still sparse. The aim of the current study was therefore to provide causal evidence for the influence of the extent of expectancy violations on extinction retention using a novel virtual reality fear conditioning paradigm.
Center of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Wuerzburg, Margarete-Hoeppel-Platz 1, Wuerzburg 97080, Germany. Electronic address:
* The study tested intermittent theta burst stimulation (iTBS) on 50 participants over three days, measuring fear responses during various learning and testing phases to see if iTBS could help reduce fear.
* Results showed that active iTBS reduced fear responses during extinction learning, but there were no significant effects observed during later recovery or reinstatement tests, indicating limited effectiveness for improving extinction memory.
Department of Psychology, Clinical Psychology, Experimental Psychopathology and Psychotherapy, Philipps University of Marburg, Gutenbergstraße 18, 35032, Marburg, Germany.
Occasionally presenting the unconditioned stimulus (US) during extinction training (occasional reinforced extinction, ORE) either unpaired or paired with the conditioned stimulus (CS) provides initial evidence for a less pronounced return of fear. However, translating this approach into clinical practice is challenging due to ethical and practical concerns of exposing patients to the original USs. The present study investigated extinction of fear responses in a novel approach employing ORE using vivid fear imagery of the US instead of actually exposing to it.
Dept. of Physiology and Pharmacology, Sapienza University of Rome, Rome 00185, Italy; Neuropharmacology Unit, IRCCS Fondazione Santa Lucia, Rome 00143, Italy. Electronic address:
Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition arising from traumatic experiences, marked by abnormal fear memories. Despite women are twice as likely as men to develop PTSD, the biological mechanisms underlying this disparity remain inadequately explored, particularly in preclinical studies involving female subjects. Previous research shows that female rats exhibit active fear responses, while males display passive behaviors.
Human touch is a powerful means of social and affective regulation, promoting safety behaviors. Yet, despite its importance across human contexts, it remains unknown how touch can promote the learning of new safety memories and what neural processes underlie such effects. The current study used measures of peripheral physiology and brain activity to examine the effects of interpersonal touch during safety learning (extinction) on the recovery of previously learned threat.
