Journal of Neuroscience publication: Seasonal Variation in the Brain µ-Opioid Receptor Availability

In this paper by Sun et al., the MOLECUBES β-CUBE and X-CUBE were used to investigate µ-opioid receptor levels and their daylenght-dependant seasonal variation in rats and shows that the µ-opioid receptor system might underlie seasonal variation in mood, sociability and other socioemotional behaviour.

Journal of Neuroscience. 2021; 41(6):1265-1273. doi:10.1523/JNEUROSCI.2380-20.2020.


Research question

Seasonal rhythms influence mood and sociability. The brain µ-opioid receptor (MOR) system modulates a multitude of sea- sonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evi- dence.


Here, we first conducted a cross-sectional study with previously acquired human [11C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability. We then investi- gated experimentally whether seasonal variation in daylength causally influences brain MOR availability in rats. Rats (six male and three female rats) underwent daylength cycle simulating seasonal changes; control animals (two male and one female rats) were kept under constant daylength. Animals were scanned repeatedly with [11C]carfentanil PET imaging.


Seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability in humans. Brain regions sensitive to daylength spanned the socioemotional brain circuits, where MOR availability peaked during spring. In rats, MOR availabilities in the brain neocortex, thalamus, and striatum peaked at intermediate daylength. Varying daylength also affected the weight gain and stress hormone levels. We conclude that cerebral MOR availability in humans and rats shows significant seasonal variation, which is predominately associated with seasonal photoperiodic variation. Given the inti- mate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior.