Brain kappa opioid receptor availability across stress and social buffering conditions: A positron emission tomography study in coppery titi monkeys.

Social connectedness strongly influences health and longevity, and adult pair bonds provide psychological benefits distinct from other social relationships. Oxytocin (OT), corticotropin-releasing hormone (CRH), and opioids play an important role in pair bond formation and maintenance. OT modulates the stress response via the hypothalamic-pituitary-adrenal (HPA) axis, while the kappa (κ) opioid system may modulate OT signaling in contexts of stress and separation. Here, 20 male and female coppery titi monkeys (Plecturocebus cupreus), a unique non-human primate model for the study of pair bonding and social buffering, were exposed to a physical stressor under three social conditions: baseline (no stressor, partner present), stress (stressor, no partner) and buffering (stressor, partner present). We predicted stress would engage the dynorphin/κ-opioid receptor system, reflected in reduced κ-opioid receptor (KOR) availability measured via [11C]GR103545 Positron Emission Tomography (PET) and lower cerebrospinal fluid (CSF) OT, whereas partner presence would attenuate this response. The social buffering effect was successfully replicated: cortisol was significantly elevated during stress relative to baseline in both sexes, with no significant difference between the buffering and baseline conditions. PET imaging revealed condition- and sex-specific differences in [11C]GR103545 binding potential across limbic regions, including the amygdala, hippocampus, and hypothalamus. Females exhibited lower CSF OT levels during stress than at baseline and Spearman correlations revealed no significant associations between plasma and CSF OT. These findings highlight the complex interactions among κ-opioid signaling, OT, and HPA axis activity during social buffering and provide preliminary evidence for region- and sex-specific KOR modulation in a pair-bonded primate model.