Chronic Glucocorticoid Exposure Induces Depression-Like Phenotype in Rhesus Macaque (Macaca Mulatta)

It has long been observed in humans that the occurrence of depressive symptoms is often accompanied by the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. The rodent experiments also showed that chronic corticosterone exposure could induce depression-like phenotype. However, rodents are phylogenetically distant from humans. In contrast, non-human primates bear stronger similarities with humans, suggesting research on primates would provide an important complement. For the first time, we investigated the effects of chronic glucocorticoid exposure on rhesus macaques. Seven male macaques were selected and randomized to glucocorticoid or vehicle groups, which were subjected to either prednisolone acetate or saline injections, respectively. The depression-like behaviors were assessed weekly, and the body weights, HPA axis reactivity, sucrose solution consumption and monoaminergic neurotransmitters were further compared between these two groups. The glucocorticoid group was not found to display more depression-like behaviors than the vehicle group until 7 weeks after treatment. Chronic glucocorticoid exposure significantly decreased the levels of cortisol determined from blood (a biomarker for acute HPA axis reactivity) but increased the hair cortisol concentrations (a reliable indicator of chronic HPA axis reactivity) compared with controls. The glucocorticoid group was also found to consume less sucrose solution than controls, a good manifestation of anhedonia. This could be possibly explained by lower dopamine (DA) levels in cerebrospinal fluid induced by chronic glucocorticoid treatment. The results presented here indicate that chronic glucocorticoid exposure could disturb both the acute and chronic HPA axis reactivity, which eventually disturbed the neurotransmitter system and led monkeys to display depression-like phenotype.