Music engages the phasic dopaminergic D1-receptor system in humans: a PET-fMRI study using [11C]SCH23390

Music listening reliably induces arousal in the listener, however its effect on dopaminergic transmission is not yet fully explored. We investigated the responsiveness of the striatal dopamine D1 receptor (D1R) system, which is preferentially engaged by phasic dopaminergic signals, using simultaneous PET-fMRI and the selective D1R radioligand [11C]SCH23390. Fifteen neurotypical participants were scanned during silence before listening to a music piece in its pleasant and unpleasantly manipulated variation. Striatal binding potential (BPND) was significantly lower when listening to music compared to silence. A seed-based fMRI analysis revealed higher functional connectivity between the striatum and left dorsolateral pre-frontal cortex (MNI: x = -43, y = 24, z = 24) during pleasant music in relation to unpleasant music. An exploratory whole-brain D1R PET analysis further identified increased insular BPND (MNI: x = -33, y = 1.5, z = 16.5; T = 5.58) during pleasant relative to unpleasant music. Comparison of BPND and fMRI beta estimates changes within that prefrontal cluster showed a moderate correlation between the pleasant and unpleasant music condition (R = -0.52, p = 0.046), but no correlation for the silent conditions (R = 0.24, p = 0.42). Changes in ratings of musical pleasantness moderately correlated with fMRI changes in the prefrontal cluster, but not with changes in BPND. Our results demonstrate that music irrespective of valence engages the D1R system, indicating that the inherently phasic nature of music can drive D1R-related responses. Furthermore, our results demonstrate valence effects in functional connectivity between the striatum and the left dorsolateral prefrontal cortex when listening to music with varying pleasantness.