Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. 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 investigated 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 intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior.

SIGNIFICANCE STATEMENT Seasonal rhythms influence emotion and sociability. The central μ-opioid receptor (MOR) system modulates numerous seasonally varying socioemotional functions, but its seasonal variation remains elusive. Here we used positron emission tomography to show that MOR levels in both human and rat brains show daylength-dependent seasonal variation. The highest MOR availability was observed at intermediate daylengths. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior.

季节性节奏会影响情绪和社交能力。大脑 μ-阿片受体 (MOR) 系统调节多种季节性变化的社会情感功能，但其季节性变化仍然难以捉摸，之前没有报道过体内证据。在这里，我们首先对先前获得的人类进行了横断面研究 [ ¹¹C]卡芬太尼 PET 成像数据（132 名男性和 72 名女性健康受试者）来测试 MOR 可用性是否存在季节性变化。然后，我们通过实验研究日长的季节性变化是否会因果影响大鼠大脑 MOR 的可用性。大鼠（六只雄性和三只雌性大鼠）经历了模拟季节变化的日长周期；对照动物（两只雄性和一只雌性大鼠）保持在恒定的光照下。^{用 [ 11}反复扫描动物C]卡芬太尼 PET 成像。季节性变化的日长与人类大脑 MOR 可用性呈倒 U 形功能关系。对日长敏感的大脑区域跨越社会情感大脑回路，其中 MOR 可用性在春季达到顶峰。在大鼠中，大脑新皮层、丘脑和纹状体中的 MOR 可用性在中间日照时达到峰值。不同的日长也会影响体重增加和应激激素水平。我们得出结论，人类和大鼠的大脑 MOR 可用性显示出显着的季节性变化，这主要与季节性光周期变化有关。鉴于 MOR 信号与社会情感行为之间的密切联系，这些结果表明 MOR 系统可能是人类情绪和社会行为季节性变化的基础。

意义声明季节性节律影响情绪和社交能力。中枢 μ-阿片受体 (MOR) 系统调节许多季节性变化的社会情感功能，但其季节性变化仍然难以捉摸。在这里，我们使用正电子发射断层扫描来显示人类和大鼠大脑中的 MOR 水平显示出依赖于日长的季节性变化。在中间日照时观察到最高的 MOR 可用性。鉴于 MOR 信号与社会情感行为之间的密切联系，这些结果表明 MOR 系统可能是人类情绪和社会行为季节性变化的基础。