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Kappa opioid receptors (KORs) have been characterized as an aversive system in the brain and implicated in social behavior in preclinical models. This work investigated the effect of social status on the KOR system in humans using positron emission tomography (PET) imaging with the novel KOR agonist radiotracer [ 11 C]EKAP. Eighteen healthy participants (mean age 41.2 ± 9.3) completed the Barratt Simplified Measure of Social Status (BSMSS), an MRI and an [ 11 C]EKAP PET scan on the High Resolution Research Tomograph. Arterial blood sampling and metabolite analysis were conducted to obtain the input function. Regions of interest were based upon an MR template and included the reward/aversion areas of the brain. The multilinear analysis-1 (MA1) method was applied to the regional time-activity curves (TACs) to calculate [ 11 C]EKAP regional volume of distribution (V T ). Mixed models and Pearson correlation coefficients were used for body mass index (BMI), gender and age, with age being dropped in subsequent analyses because of nonsignificance. An overall effect of primary ROIs (F 7, 112 7.43, p &lt; 0.0001), BSMSS score (F 1, 13 7.45, p = 0.02), BMI (F 1, 13 23.5, p &lt; 0.001), and gender (F 1, 13 23.75, p &lt; 0.001), but not age (F 1, 13 1.12, p = 0.35) was observed. Regional [ 11 C]EKAP V T and BSMSS were found to be negatively correlated in the amygdala (r = -0.69, p &lt; 0.01), anterior cingulate cortex (r = -0.56, p = 0.02), caudate (r = -0.66, p &lt; 0.01), frontal cortex (r = -0.52, p = 0.04), hippocampus (r = -0.60, p = 0.01), pallidum (r = -0.59, p = 0.02), putamen (r = -0.62, p = 0.01), and ventral striatum (r = -0.66, p &lt; 0.01). In secondary (non-reward) regions, correlations of [ 11 C]EKAP V T and BSMSS were nonsignificant with the exception of the insula. There was an inverse correlation between social status and KOR levels that was largely specific to the reward/aversion (e.g., saliency) areas of the brain. This finding suggests the KOR system may act as a mediator for the negative effects of social behaviors in humans.

Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers