The effect of urethane on pituitary-adrenal function of female rats

Urethane anaesthesia resulted in rapid and sustained increase in plasma corticosterone levels of adult female rats both in the (a.m.) AM and (p.m.) PM. Initial corticosterone levels of non-injected control rats showed marked AM-PM differences (i.e., 28.3 micrograms/dl and 52.6 micrograms/dl, respectively), but by 10 min post-injection, the morning corticosterone levels were increased (76.2 micrograms/dl) such that AM-PM differences were not observed. By 30 min post-injection, PM plasma corticosterone levels had increased significantly (88 micrograms/dl) but were not different from AM values for the remainder of the 2 h experiment. Saline injected controls showed the expected response to stress; plasma corticosterone levels were increased (P less than 0.01) at 10 min but were back to baseline by 45 min (9.0 micrograms/dl). Dexamethasone (100 micrograms/kg, sc) markedly suppressed both AM and PM urethane-stimulated corticosterone levels. However, diurnal differences in dexamethasone suppression were noted; whereas morning plasma corticosterone levels averaged 24.8 micrograms/dl over the five sampling times corresponding PM values averaged 54.3 micrograms/dl. Plasma corticosterone levels of non-anaesthetized, hypophysectomized ACTH-primed and injected rats were not different from those similarly treated and anaesthetized with urethane and urethane-induced increases in corticosterone were not abolished by hypothalamic isolation (HI). However, plasma corticosterone levels of HI rats were less than those of sham-operated controls (i.e., 58 micrograms/dl and 74 micrograms/dl, respectively). Collectively, these data indicate that urethane evokes a sustained increase in pituitary-adrenal activity, that the increased activity is dexamethasone sensitive and that a site of action for pituitary-adrenal activation is, at least in part, at the level of the hypothalamo-hypophyseal complex.