Estradiol Treatment in a Nonhuman Primate Model of Menopause Preserves Affective Reactivity

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Abstract

Human affective life changes with age, becoming more positive and less negative in later life. This change occurs even as aging leads to declines in health and cognitive outcomes. Despite these well-documented effects in humans, the extent to which affective processes change as a result of aging in nonhuman animals, particularly nonhuman primates, is unclear. As a first step toward developing an animal model for human affective aging, we tested aged, surgically menopausal aged and middle-aged gonadally intact female rhesus monkeys (Macaca mulatta) on a classic index of affective reactivity in monkeys, the Human Intruder Task. The Human Intruder Task evaluates behavioral responses to varying levels of threat. Aged, surgically menopausal monkeys received hormone replacement therapy consisting of a cyclic estradiol regimen or vehicle injections as a control. Average responsivity to threat did not vary by condition, but middle-aged monkeys and aged monkeys on estradiol were more reactive to the most potent level of threat than to a moderate level of threat, replicating previously published results in other age groups and male monkeys. In contrast, aged monkeys who were not on estradiol did not show such calibration to threat level. These findings suggest that estrogen may be important for maintaining more youthful affective responding. They also illustrate the utility of behavioral assays of affective reactivity in nonhuman primate models of cognitive and reproductive aging in humans.

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