Almeida, A. J. D.; Hobson, B. A.; Savidge, L. E.; Manca, C.; Paulus, J. P.; Bales, K. L.; Chaudhari, A. J.

Purpose: The kappa opioid receptor (KOR) plays a pivotal role in stress- and anxiety-related behaviors, especially in social separation and bonding. However, KOR modulations in these social contexts are not fully characterized. The coppery titi monkey (Plecturocebus cupreus) has been utilized as a translational animal model for studying the neurobiology of attachment, as they form socially monogamous adult pair bonds. While the PET radiotracer 11C-GR103545 has shown the ability to track KOR activity in other species, it has not been utilized in titi monkeys. This study assessed 11C-GR103545 PET for characterizing KOR activity in vivo and its pharmacological blockade in titi monkeys. Methods: Adult titi monkeys (N=6) underwent 11C-GR103545 PET brain scans at baseline, followed by repeat scans upon administration of a KOR antagonist (CERC-501) and a KOR agonist (U50,488). Region-specific, non-displaceable binding potential (BPND) was calculated, with the cerebellum as the reference region, focusing on 14 brain volumes of interest (VOIs) implicated in social bonding. Results: Baseline 11C-GR103545 uptake characteristics across VOIs were consistent with previous reports in humans and other monkey models. CERC-501 pretreatment led to a significant reduction in BPND (average 55.99%) across several, but not all brain VOIs, with the most notable reduction in the superior frontal gyrus (76.25%). In contrast, U50,488 pretreatment resulted in no significant BPND changes across the VOIs analyzed. Conclusions: This study demonstrates the utility of 11C-GR103545 to assess KOR binding dynamics in a monkey model of social bonding. Region-specific blockade of KOR was observed after pretreatment by CERC-501, while blockade by the KOR agonist U50,488 did not change 11C-GR103545 binding.