Investigation of depression-like phenotypes and their behavioral correlates in cynomolgus monkeys (Macaca fascicularis).

Abstract

BACKGROUND: The global burden of depression is heavy, with unclear pathogenesis, relying on animal models for researching neural mechanisms and treatments. Existing rodent models lack social attributes, while non-human primate models (such as the natural depression model in cynomolgus monkeys) are closer to human social stress scenarios. Previously, the screening of natural depression models in cynomolgus monkeys was unvalidated and their causes were unclear. This study constructs a cynomolgus monkey community by simulating wild environments, records social behaviors, and explores the causes of their natural depression-like behaviors, analyzes their correlations with exploratory/social behaviors, providing behavioral evidence for phenotype-behavior links in this model. RESULTS: The conflict behaviors in the community were recorded to develop a conflict behaviors matrix, and the behaviors of all individuals were monitored by using the focus observation method. The analysis entailed two complementary approaches: (1) recording and analyzing ten behaviors across ten observation time slots for depressive individuals (defined by persistent core depression-like behaviors: crouching, head-bowing, and slumped posture with open eyes); and (2) comparing high- and low-ranking groups to identify social stressors driving these behaviors. The David Scoring (DS) scores of the animals were determined based on the record of conflict behaviors in the community. The individuals were divided into high- and low-ranking groups, and the daily behaviors of the two groups were analyzed. The results showed statistically significant differences in depression behaviors, anxious behaviors, and motor behaviors among the monkeys. Further, individuals with depression behaviors exhibited drastically lower capability in exploration and social interaction. Additionally, social frustration stress responses induced by inter- and intra-community conflict behaviors may account for this behavior in the cynomolgus monkey model of natural depression. CONCLUSIONS: The natural depression model of caged Macaca fascicularis is a social defeat model induced by yield-attack behavior.