Dopamine D2/3 receptors and functional connectivity during fear extinction: A PET-fMRI study.

Overview

1. Department of Medical Sciences, Experimental Cognitive and Affective Neuroscience Lab, Uppsala University, Uppsala, Sweden
2. Department of Psychology, Uppsala University, Uppsala, Sweden
3. Department of Psychology, Lund University, Lund, Sweden
4. Molecular Imaging and Medical Physics, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
5. Department of Pedagogy, Psychology and Social Work, Mid Sweden University, Östersund, Sweden

Abstract

Background: The ability to learn what is dangerous in the environment and what no longer exerts a threat is essential for survival. The latter process is studied using Pavlovian fear extinction, the repeated presentation of a feared stimulus that gradually attenuates the fear response. Dysregulation of the extinction process is implicated in a range of anxiety disorders, yet the neurobiological mechanisms supporting extinction learning in humans remain incompletely mapped, particularly with respect to the modulating role of dopamine.

Objective: To examine the role of baseline dopamine D2/3 receptors in fear extinction and responses to unconditioned stimulus (US) omission.

Materials and methods: Fifteen healthy adults completed a differential cued Pavlovian conditioning paradigm, including one conditioned stimulus (CS+) paired with an aversive electric shock US and one never paired (CS−). Participants underwent [11C]raclopride positron emission tomography (PET) of baseline dopamine D2/3 receptor availability prior to fear acquisition, and subsequent fear extinction with skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) continuously recorded.

Results: SCR and neural activations indicated remaining conditioned responding during extinction, with greater responses to CS+ than to CS− in the insula and frontoparietal regions. Higher baseline dopamine D2/3 receptor availability in the amygdala was associated with lower fear-related (CS+> CS−) connectivity between the right amygdala and the right anterior insula. Higher differential SCR (CS+> CS−) was associated with reduced functional connectivity between the right amygdala and left anterior insula. Lower baseline dorsal striatal D2/3 receptor availability was associated with greater mean SCRs to US omission. No associations were detected between baseline D2/3 receptor availability and extinction-related reductions of conditioned SCR or neural responses across trials.

Conclusion: These findings suggest that individual differences in dopamine D2/3 receptor availability are related to threat processing and responses to US omission, but may be less strongly associated with extinction learning itself.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Due to the sensitive nature of the data collected in this study, raw data will not be shared. Processed data and code will be shared upon reasonable request.

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Version 3, 28 September 2026

• Authors: added Ashika Anne Roy (0000-0001-9396-077X); Andreas Frick (0000-0003-2516-9075); removed Ashika Anne Roy; Andreas Frick

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 6 keywords, 3 funders, 70 references, 2 RRIDs.

Cite

This paper

Roy, A. A., Vegelius, J., Björkstrand, J., Lubberink, M., Fredrikson, M., Åhs, F., & Frick, A. (2026). Dopamine D2/3 receptors and functional connectivity during fear extinction: A PET-fMRI study. Neuroimage. Reports, 6(4), 100402. https://doi.org/10.1016/j.ynirp.2026.100402

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