Stress reduces brain KOR availability and CSF oxytocin in titi monkeys; social buffering attenuates.

Social connectedness and pair bonds are vital for health, offering unique psychological benefits. Oxytocin (OT), corticotropin-releasing hormone (CRH), and opioids are central to pair bond dynamics. OT regulates the HPA axis and stress response. The kappa (κ) opioid system is hypothesized to modulate OT signaling, particularly during stress and separation. Understanding the interplay between KOR, OT, and HPA axis activity during social buffering in a relevant primate model is crucial to elucidate the neurobiological underpinnings of social support and stress resilience.

Researchers exposed 20 male and female coppery titi monkeys (Plecturocebus cupreus) to a physical stressor under three conditions: baseline (no stressor, partner present), stress (stressor, no partner), and buffering (stressor, partner present). They measured κ-opioid receptor (KOR) availability via [11C]GR103545 PET imaging and CSF oxytocin (OT) levels. Cortisol was also assessed as a stress marker. The primary endpoint was to observe changes in KOR availability and OT levels in response to stress and social buffering, with a focus on limbic regions.

The study successfully replicated the social buffering effect, with cortisol significantly elevated during stress compared to baseline in both sexes, and no significant difference between buffering and baseline conditions. PET imaging of [11C]GR103545 binding potential revealed condition- and sex-specific differences in kappa opioid receptor (KOR) availability across key limbic regions, including the amygdala, hippocampus, and hypothalamus. These findings align with the prediction that stress engages the dynorphin/κ-opioid receptor system. > Females specifically exhibited lower CSF oxytocin (OT) levels during stress compared to baseline, highlighting a sex-specific neuroendocrine response. Spearman correlations showed no significant associations between plasma and CSF OT, suggesting distinct peripheral and central OT dynamics. These findings indicate complex interactions among κ-opioid signaling, OT, and HPA axis activity during social buffering.