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bioRxiv · 10.64898/2026.07.30.739761

Endogenous Opioid System Modulates Neural Activation During Emotion Regulation

Putkinen, V. J.·Ravindran, A.·Seppala, K.·Harju, H.·Song, A.·Nummenmaa, L.
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Abstract

Emotion regulation is critical for adaptive functioning and mental health. Functional neuroimaging studies have identified distributed frontal, parietal, and limbic networks involved in emotion regulation, particularly during cognitive reappraisal. However, the neurochemical mechanisms underlying individual differences in emotion regulation remain poorly understood. The endogenous opioid system is a promising candidate because -opioid receptor systems acts as a stress buffer and modulates emotional responses to both rewarding and aversive stimuli We used positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to examine whether baseline -opioid receptor (MOR) availability is associated with haemodynamic responses during emotion regulation through reappraisal. Participants underwent [11C]carfentanil PET imaging to quantify MOR availability and subsequently completed an fMRI task involving passive viewing of emotional images and cognitive reappraisal of their emotions during image viewing As expected, fMRI revealed engagement of the dorsolateral prefrontal cortex and inferior parietal lobule during cognitive reappraisal. Baseline MOR availability predicted blood oxygenation level-dependent (BOLD) responses in frontal, temporal, and parietal regions: individuals with higher MOR availability showed a larger difference between regulation and viewing trials in the temporal pole, angular gyrus, anterior insula, thalamus, and inferior frontal gyrus. These associations were driven primarily by stronger responses during passive viewing, although some regions also showed evidence of reduced responses during active reappraisal. These findings suggest that higher endogenous opioid tone is associated with stronger recruitment of distributed frontal, temporal, and parietal networks during emotional stimulus processing as well as attenuation of activity in some of these regions during cognitive reappraisal. Thus, while higher MOR availability is associated with enhanced neural responsiveness to emotional stimuli, these responses can nevertheless be effectively modulated through deliberate emotion regulation.

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Putkinen, V. J., Ravindran, A., Seppala, K., Harju, H., Song, A., Nummenmaa, L.. 2026-08-04. Endogenous Opioid System Modulates Neural Activation During Emotion Regulation. https://doi.org/10.64898/2026.07.30.739761

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