Neonatal orbital frontal damage alters basal cortisol and emotional reactivity, but not stress reactive cortisol response, in adult rhesus monkeys

Abstract

Rationale : Rodent studies indicate that the orbital and medial prefrontal cortex have an inhibitory control on the hypothalamic–pituitary–adrenal (HPA) axis, by restraining the acute stress response and facilitating negative feedback inhibition, which can also affect its basal tone of activity. Similarly in humans, extent of damage to the medial prefrontal cortex correlates negatively with cortisol levels. However, lesions of the orbital frontal cortex (OFC) in adult monkeys resulted in no effects on HPA activity. In the present study, we assessed the effects of neonatal OFC lesions on emotional and HPA reactivity to an acute stressor. Methods : Subjects received bilateral aspiration lesions of orbital frontal areas 11 and 13 (Neo-Oasp, n=5) or sham operations (Neo-C, n=6) between 7 and 14 days of age. Upon reaching adulthood (6–8 years), emotional responses were examined using the Human Intruder (HI) paradigm given at 7: 00 hr for all animals and blood samples were collected immediately before and after the stressor to assess HPA axis reactivity. Two days prior to the HI test, two blood samples were collected at the same time of day but without the stressor. Diurnal cortisol rhythm was assessed one year later with blood samples collected at Lights-On (7:00 hr), Mid-day (13:00hr), and Lights-Off (19:00hr). Results : In the presence of the HI, Neo-Oasp animals exhibited less species typical defensive freezing responses as compared to controls (Group: F[1,9] = 14.43, p=0.004), yet they exhibited more hostility throughout the test (Group: F[1,9] = 5.45, p=0.044). Groups did not differ in their neuroendocrine response to the HI, showing a significant increase in cortisol after the stressor as compared to baseline (F[1,9] = 22.08, p=0.001). To control for individual variability and determine that changes in hormone levels were not due to handling or sampling technique, blood samples taken without the stressor revealed that Neo-Oasp animals exhibited lower cortisol at Lights-On compared to Neo-C animals (F[1,9] = 6.01, p=0.037). This lower basal HPA activity was also observed when the diurnal cortisol rhythm was later investigated in the same animals (Group×Time of Day F[2,18] = 3.81, p=0.042). Conclusion : Results indicate that OFC damage in infancy alters emotional behaviors as well as basal but not stress reactive HPA axis function.

Keywords

• stress
• cortisol response
• orbital frontal cortex
• HPA activity
• emotional reactivity