Stress through handling for vaginal screening, serotonin, and ACTH response to ether

The effect of duration of handling for vaginal smear screening on the adrenal weight and acute ACTH response to ether were examined in 4-day-cycling female rats, sacrificed at 97-103 days of age on diestrus-2 after evaluation of resistance to handling, thymus weight, and hypothalamic serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). Prolonged handling paralleled increased resistance (behavioral response) to handling and adrenal weight but was inversely related to thymus weight. The hypothalamic 5-HT, 5-HIAA, and 5-HIAA/5-HT ratio, compared to controls with similar conditions of handling, were not modified after 2.5 min of ether despite the ACTH rise. In ether-stressed rats, the ACTH response to ether was lower after prolonged handling compared to short handling paralleling decreased thymus weight. In contrast, 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio were higher, paralleling increased resistance and adrenal weight. The results suggest chronic activation of the hypothalamo-pituitary-adrenal axis with positive serotonergic involvement after prolonged handling and resistance during vaginal screening and a negative implication of this activation on the acute ACTH response to ether.