Oxytocin modulates behavioral and physiological responses to a stressor in marmoset monkeys

Abstract

Social isolation is a major source of stress and can lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis. The presence of a close social partner can reduce the magnitude of the HPA-axis response during a stressor, a phenomenon known as social buffering. The oxytocin (OXT) system has been identified as one candidate for mediating social buffering due to its role in the facilitation of social bonding and the expression of prosocial behavior. The goal of the present study was to determine whether the OXT system contributes to social buffering of HPA-axis activity in response to stressor exposure in marmoset monkeys (Callithrix jacchus). Male and female marmosets experienced a standardized psychogenic stressor with and without their long-term mate under OXT-treatments (Pro(8)-OXT, Leu(8)-OXT, OXT antagonist, and saline); we assessed HPA-axis activity by measuring urinary cortisol across the stressor. We found that blocking, but not augmenting, the OXT system altered patterns of cortisol and proximity behavior in response to a stressor. We demonstrated that (1) the presence of a mate during a stressor significantly attenuated HPA-axis activity in female, but not male, marmosets; (2) male, but not female, marmosets treated with an OXT antagonist had significantly higher HPA-axis activity across the stressor than when they were treated with saline, suggesting that the OXT system may reduce the stressor-induced rise in cortisol levels; (3) male and female marmosets treated with an OXT antagonist spent significantly less time in close proximity to their mate during the first 30 min of the stressor than when they were treated with saline, suggesting that the OXT system may be important for the expression of partner-seeking behavior during a stressor. Thus, the OXT system and social context differentially influenced how the HPA-axis responded to a stressor in male and female marmosets, and may modulate HPA-axis activity by promoting the expression of proximity behavior with a close social partner.

Keywords: Cortisol; HPA-axis; Pro(8)-OXT; Proximity; Social buffering; Stress.

Fig. 1

Schematic of basic and derived measures of HPA-axis activity to a standardized psychosocial stressor in marmosets (adapted with permission; French et al., 2012). Baseline = mean first-void cortisol concentration from Days 1–3 (stressor occurred on Day 3). Post = mean first-void cortisol concentration from Days 4–6. Reactivity = maximum cortisol concentration during stressor—Baseline. Regulation = Post—Baseline. Area Under Curve-ground (AUC_g) = areaunder the cortisol response curve with respect to a cortisol concentration of 0 µg/mg creatinine. AUC_i = area under the cortisol response curve with respect to Baseline. ^aAdministration of oral OXTA or saline; ^bAdministration of intranasal Pro⁸-OXT, Leu⁸-OXT, or saline; ^c30-min videotaped observation; ^dReunion with pair-mate in home enclosure.

Fig. 2

Mean (±SEM) cortisol levels across the stressor period in male and female marmosets (n = 10), collapsed across OXT-treatment. Reunion = Mean cortisol 1–2 h post-reunion. a > b > c > d at p < 0.05.

Fig. 3

Mean values (±SEM) for components of the stress response in female and male marmosets (n = 10): (A) Reactivity, (B) AUC_g, (C) AUC_i, and (D) Regulation for marmosets that experienced a stressor with and without their partner. ^*p < 0.05, ^#p < 0.06. (E) Reactivity, (F) AUC_g, (G) AUC_i, and (H) Regulation for marmosets that received an OXT-treatment: Marmoset OXT agonist (Pro⁸-OXT); Consensus mammalian OXT agonist (Leu⁸-OXT); saline; OXT antagonist (OXTA: L368,899^®). a > b at p < 0.05, ^#p < 0.10.

Fig. 4

Mean (±SEM) time spent in proximity to the adjacent enclosure during the first 30 min of the stressor for marmosets (n = 10) that that received an OXT-treatment, and experienced a stressor with and without their partner. a > b at p < 0.05, ^#p < 0.10.