Intranasal oxytocin treatment does not attenuate the hypothalamo-pituitary-adrenal axis in beef heifers subjected to isolation stress or restraint and isolation stress

Abstract

Changes in the physiological, psychological, and behavioral manifestations of stress have been observed in association with increases in circulating oxytocin (OXT). Providing OXT intranasally has been shown to attenuate stressor-induced hypothalamo-pituitary-adrenal (HPA) axis activation in humans and rodents; however, anxiolytic effects may be context and species specific. The present study aimed to investigate the effect of intranasal OXT supplementation on stressor-induced activation of the HPA axis in beef cattle. We hypothesized that OXT would attenuate activation of the HPA axis, ultimately decreasing plasma cortisol and adrenocorticotropic hormone (ACTH). Twenty-eight Bos taurus heifers were blocked by bodyweight and randomly allocated to one of four treatment groups, in a 2 × 2 factorial arrangement: (1) saline, isolated, standing, and unrestrained (S-isolation stress [IS], 0.015 mL/kg BW 0.9% isotonic saline, n = 7); (2) saline, isolated, and restrained (S-restraint and isolation stress [RIS]; 0.015 mL/kg BW 0.9% isotonic saline; n = 7); (3) OXT, IS (OXT-IS, 0.3 IU/kg BW oxytocin; n = 7); and (4) OXT and RIS (OXT-RIS, 0.3 IU/kg BW oxytocin; n = 7). Oxytocin and saline were administered intranasally. Intranasal treatments were given followed by a waiting time of 30 min when each of the stress treatments was applied for 2 h. Blood samples were collected via jugular catheters directly after stressor application and every 10 min thereafter, for 2 h. Cortisol concentrations increased over time in animals exposed to RIS (P < 0.01) and decreased over time in animals exposed to IS (P < 0.01). Concentrations of ACTH decreased over time for the IS-treated heifers but remained elevated for the RIS-treated heifers (P < 0.01). Under the conditions of the present study, OXT treatment did not affect measured indicators of HPA axis activation. A treatment × time interaction (P < 0.01) was detected for OXT, such that OXT heifers exhibited greater initial OXT concentrations followed by a decline; saline-treated heifers had consistently stable oxytocin concentrations. The RIS-treated heifers increased their glucose (P < 0.01) and lactate (P < 0.01) concentrations throughout the application of the stressors compared with the IS-treated heifers. Overall, restraint stress increased cortisol and oxytocin in B taurus heifers compared with heifers subjected only to isolation. Finding a more intermediate stress model may better allow for detection of the effects of oxytocin on the stress response.

Keywords: Anxiety; Anxiolytic; Cattle; HPA axis.