The Use of Guanfacine to Mediate Anxiety-related Reactivity and Reduce Associated Agonistic Behavior in Two Pigtail Macaques (Macaca nemestrina)

Abstract

Guanfacine, an α 2adrenoceptor agonist, has been used to successfully treat self-injurious behavior in nonhuman primates, including macaques (Macaca mulatta) and baboons (Papio anubis). It does so by facilitating a correction to the dopaminergic system that mediates a reduction in impulsivity and reactivity. Given this, we assessed the potential efficacy of guanfacine to treat socially directed agonistic behavior in primates with an apparent reactive behavioral phenotype. We present data from 2 pigtail macaques (Macaca nemestrina): an intact adult male housed in a breeding group, and an experimentally naive adult female living in a research setting with her social partner. Baseline behavioral assessments suggested that both macaques showed extreme responses to external stressors that triggered them to aggress social partners often leading to wounding that required veterinary intervention. Both animals were tracked during the course of 1 y. Once treated regularly with guanfacine, both animals showed significant reduction in their agonistic behavior and the rate at which they wounded other animals. Indeed, in the year since the female has been treated with guanfacine she has never wounded her cagemate. By collecting regular and detailed behavioral observations on the male in the breeding colony, we were able to identify triggers for his aggression and to track the behavioral changes evidenced after guanfacine treatment. These data supported our hypothesis that his aggression reflected extreme reactivity to external stressors, rather than general anxiety. Importantly, we saw only a limited and short-lived reduction in the male's affiliative behavioral rates, and thus guanfacine had no sedative effect, but did successfully reduce his reactivity and resultant agonism and wounding.