Pleasurable music activates cerebral µ-opioid receptors: a combined PET-fMRI study

• Published in: European journal of nuclear medicine and molecular imaging Vol. 52; no. 10; pp. 3540 - 3549
• Main Authors: Putkinen, Vesa, Seppälä, Kerttu, Harju, Harri, Hirvonen, Jussi, Karlsson, Henry K., Nummenmaa, Lauri
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2025; Springer Nature B.V
• Subjects: Adult; Agonists; Binding; Brain - diagnostic imaging; Brain - metabolism; Brain - physiology; Cardiology; Chills; Emotions; Experiments; Female; Fentanyl - analogs & derivatives; Functional magnetic resonance imaging; Headphones; Heart rate; Hemodynamic responses; Hemodynamics; Humans; Hypotheses; Imaging; Magnetic Resonance Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Multimodal Imaging; Music; Narcotics; Neostriatum; Neuroimaging; Nuclear Medicine; Nucleus accumbens; Oncology; Opioid receptors; Original; Original Article; Orthopedics; Pleasure; Positron emission; Positron emission tomography; Prefrontal cortex; Radiology; Receptors; Receptors, Opioid, mu - metabolism; Reinforcement; Sensorimotor system; Young Adult; Pleasure; MOR; fMRI; Music; Endogenous Opioids; PET
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-025-07232-z

Purpose The μ-opioid receptor (MOR) system mediates incentive motivation and the hedonic component of primary rewards such as food and sex. However, there is no direct in vivo evidence for the involvement of the MOR system in pleasure derived from aesthetic rewards such as music.  Methods We measured MOR availability with positron emission tomography (PET) and the agonist radioligand [ 11 C]carfentanil with high affinity for MORs during the listening of pleasurable music and neutral baseline condition. Haemodynamic responses associated with dynamic pleasure ratings during listening to music and control stimuli were measured using functional magnetic resonance imaging (fMRI). Results The PET results revealed that pleasurable music increased [ 11 C]carfentanil binding in several cortical and subcortical regions, including ventral striatum and orbitofrontal cortex, known to contain “hedonic hotspots”. [ 11 C]carfentanil binding in the nucleus accumbens during the music condition was associated with number of pleasurable chills, linking the subjective experience of pleasure to striatal opioid release. Individual variation in baseline MOR tone influenced pleasure-dependent haemodynamic responses during music listening in regions associated with interoceptive, sensorimotor, and reward processing. Conclusions These findings provide the first neuroimaging evidence that pleasurable music modulates MOR system function. The results indicate that the μ-opioid system governs complex aesthetic rewards in addition to biologically essential primary rewards.