Separation Induced Changes in Squirrel Monkey Hypothalamic-pituitary-adrenal Physiology Resemble Aspects of Hypercortisolism in Humans

When separated from groups, squirrel monkeys respond with significant increases in plasma cortisol and adrenocorticotropic hormone (ACTH). While cortisol remains elevated above pre-separation levels, significant reductions occur in ACTH. Monkeys that respond with greater increases in cortisol subsequently exhibit greater reductions in ACTH, which suggests that reductions in ACTH are mediated by corticosteroid feedback. Monkeys that respond with greater increases in cortisol also tend to exhibit greater cerebrospinal fluid levels of the dopamine metabolite HVA, but not the norepinephrine metabolite MHPG, or corticotropin-releasing factor (CRF). Attenuation of corticosteroid feedback with metyrapone results in significant increases in circulating ACTH, and in older monkeys increases plasma HVA. Similar findings in humans have been reported in clinical studies of hypercortisolism and major depression.