Estradiol treatment in a nonhuman primate model of menopause preserves affective reactivity

Abstract

This phenomenon, known as the positivity effect (or positivity bias), occurs even as aging leads to declines in health and cognitive outcomes. Despite these well documented effects in humans, extent to which affective processes change in nonhuman animals, and in particular nonhuman primates -is unclear. As a first step towards developing a model for human affective aging in rhesus monkeys (Macaca mulatta), we tested aged, surgically menopausal aged and middle-aged gonadally intact female rhesus monkeys 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 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.

Shifting sociality during primate ageing

“…In animals, parallel shifts in the valence of behavioural interactions can therefore be assessed by examining the relative frequency of negative social interactions (such as aggression given) compared with positive interactions (such as grooming given). Finally, some work has experimentally tested animals' attention or responses to emotionally valanced information [47,48], more closely mirroring human experimental work looking at attentional biases.…”

“…Similarly, older Barbary macaques [18,23], long-tailed macaques [32], bonnet macaques [38] and Japanese macaques [24,27,29,30] also show declines in grooming given but initiate aggressive behaviours like younger adults. Macaques show similar shifts in their production of and responses to negative emotional signals or contexts: the production of negative emotional signals such as yawning and scratching increases in older adults [32]; production of conspecific threat signals generally stays consistent or increases in adult animals [42,50]; and older macaques can show exacerbated responses to external threats in controlled experiments [47]. This aligns with converging experimental evidence looking at cognitive biases, showing that older macaques attend relatively more to negative socioemotional stimuli (photographs of conspecific threat faces) compared with neutral or positive expressions [48], similar to human research measuring looking responses to affective stimuli using similar paradigms [51,52].…”

Social Housing Status Impacts Rhesus Monkeys’ Affective Responding in Classic Threat Processing Tasks

“…To understand what was driving the significant interaction, we analyzed responses in the profile and stare conditions separately, as monkeys are often not reactive during profile [40]. As expected, reactivity was low during the profile conditions and there was not a significant effect of housing condition ( were much more reactive in stare near than stare far, while socially-housed monkeys showed very similar reactivity across these two conditions.…”

“…Eighteen monkeys participated in one of two variants of the Human Intruder Test (HIT; see Table 1). Monkeys were tested individually in a standard primate cage (60 cm x 75 cm x 75 cm) and were exposed to an unfamiliar experimenter in four different conditions after a one-minute acclimation period as described previously by our group (e.g., [39,40,48,49]) and others (e.g., [41]). The four conditions were presented in the following order: 1) profile far: person facing 90 degrees away from the cage at 1 m distance;…”

“…To assess the potential role of social context effects on behaviors commonly used to characterize changes in psychosocial health (including features related to depression and anxiety and other neurodevelopmental disorders), we analyzed responses of four cohorts of healthy adult rhesus macaques housed in various social configurations. Monkeys completed a test of responsivity to ostensibly threatening objects (as in [37][38][39]) and the Human Intruder Test (as in [40][41][42]). Here, we capitalize upon methodological consistency across cohorts (including standardized protocols for observation, interrater reliability, etc.…”