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

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 [ 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.