CHRONIC MELATONIN TREATMENT COUNTERACTS GLUCOCORTICOID-INDUCED DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE RAT

Transient exposure of rats to high doses of dexamethasone (DEX; 500 mu g/day for 5 days) produced a host of symptoms that are indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, such as incre ased adrenocortical secretion over 24 h, blunted and prolonged secreto ry,response to emotional stress, refractoriness of adrenocorticotropin in vitro release to stimulation with the secretagogues corticotropin- releasing hormone (CRH) and vasopressin, decreased levels of mRNA enco ding type II corticosteroid receptors in the hippocampus and increased numbers of transcripts encoding CRH in the paraventricular nucleus. D aily administration of melatonin (MEL; 80 mu g/kg) concomitantly with, and for 5 days after discontinuation of, glucocorticoid treatment 'no rmalized' most of the symptoms of impaired HPA regulation caused by th e exposure to DEX, While none of the treatments used caused major shif ts in circadian patterns of corticosterone secretion, MEL administrati on was associated with diminished overall corticosterone secretion and increased sensitivity to glucocorticoid feedback. Taken together, the se findings indicate that chronic MEL treatment may protect several re gulatory components of the HPA axis from glucocorticoid-induced deteri oration.