Original ArticleEffects of Interferon-Alpha on Rhesus Monkeys: A Nonhuman Primate Model of Cytokine-Induced Depression
Section snippets
Animals
Four male (5–10 kg) and 4 female (5–7 kg), rhesus monkeys (Macaca mulatta), aged 4–6 years, were housed in same-sex, dominate–subordinate pairs either together (n = 6) or individually in adjacent cages (n = 2). Social status (dominant vs. subordinate) was stable throughout the study and was based on experimenter interactions, competition for hand-fed treats, mounting, and occasional aggression. Animals were fed Purina monkey chow twice daily and were maintained on a 7 am–7 pm light–dark cycle.
Behavioral Changes
Repeated-measures ANOVAs indicated that, compared with saline, monkeys treated with IFN-alpha exhibited increased anxiety-like behaviors [F(1,7) = 7.81, p < .05] and decreased environmental exploration [F(1,7) = 10.21, p < .05] with no significant effects of time or a treatment by time interaction (Figure 1A,1B). Post hoc analyses revealed significantly increased anxiety-like behaviors at weeks 1 and 4 (p < .05), whereas exploratory behaviors were not significantly different between IFN-alpha
Discussion
Compared with saline, administration of IFN-alpha to rhesus monkeys was associated with immune, neuroendocrine, and behavioral responses similar to that observed in humans. Behavioral changes included depressive-like huddling behavior (three of eight monkeys), increased anxiety-like behavior, decreased environmental exploration, and alterations in locomotor activity that depended on social status. IFN-alpha administration was also associated with increased plasma ACTH, cortisol, and IL-6, which
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