Background: Major Depressive Disorder represents a prevalent and critical mental health issue that highlights the pressing need for innovative therapeutic solutions. Recent research has identified dysfunction within the glutamate system as a crucial element influencing both the onset and management of depressive symptoms. Although TAK-653 is a new positive allosteric modulator of AMPA receptors, its effects have not been rigorously examined in models of depression in primates. Methods: To assess its potential antidepressant properties, a chronic unpredictable mild stress protocol was implemented over 12 weeks to create a monkey model of depression, followed by a two-week treatment period with TAK-653. Results: Behavioral evaluations showed that following stress exposure, the monkeys exhibited reduced motivation for food, increased huddling, diminished movement, and a tendency to remain at the lower levels of their enclosure. They also displayed heightened anxiety in response to external stimuli. Plasma analyses indicated higher levels of cortisol, IL-6, and IL-8 in the stressed monkeys compared to baseline readings, confirming the efficacy of the stress-inducing protocol. Post-treatment with TAK-653 resulted in significant improvements, such as enhanced motivation for food, less huddling behavior, greater activity, and a move towards the upper areas of the enclosure. Additionally, the plasma analysis revealed a marked decrease in cortisol and IL-6 levels, along with an increased expression of BDNF. Conclusions: These findings indicate that TAK-653 effectively alleviates depression-like behaviors in nonhuman primate models, thereby paving the way for a promising new strategy in the treatment of depression.

Non-human primates (NHPs) are extensively utilized to investigate the neural mechanisms underlying face processing; however, measuring their brain activity necessitates a diverse array of technologies. Pupillometry emerges as a convenient, cost-effective, and non-invasive alternative for indirectly assessing brain activity. To evaluate the efficacy of pupillometry in assessing facial and emotional processing in NHPs, this study designed a face fixation task for experimental monkeys (Rhesus macaque) and recorded variations in their pupil size in response to face images with differing characteristics, such as species, emotional expression, viewing angles, and orientation (upright vs. inverted). All face images were balanced with luminance and spatial frequency. A sophisticated eye-tracking system (Eye-link 1000 plus) was employed to observe the pupils and track the viewing trajectories of monkeys as they examined images of faces. Our findings reveal that monkeys exhibited larger pupil sizes in response to carnivore faces (versus human faces, p = 0.035), negative conspecific faces (versus human faces, p = 0.018), and profile viewing angles (versus frontal view angles, p = 0.010). Notably, pupil size recorded during the 500–1000 ms post-stimulus interval was negatively correlated with their gaze durations directed at those images (r = −0.357, p = 0.016). Overall, this study demonstrates that pupillometry effectively captures subtle differences in facial and emotional processing, underscoring its potential as a valuable tool in future cognitive research and the diagnosis of disorders.