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 microg/day for 5 days) produced a host of symptoms that are indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, such as increased adrenocortical secretion over 24 h, blunted and prolonged secretory 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 encoding type II corticosteroid receptors in the hippocampus and increased numbers of transcripts encoding CRH in the paraventricular nucleus. Daily administration of melatonin (MEL; 80 microg/kg) concomitantly with, and for 5 days after discontinuation of, glucocorticoid treatment 'normalized' most of the symptoms of impaired HPA regulation caused by the exposure to DEX. While none of the treatments used caused major shifts in circadian patterns of corticosterone secretion, MEL administration was associated with diminished overall corticosterone secretion and increased sensitivity to glucocorticoid feedback. Taken together, these findings indicate that chronic MEL treatment may protect several regulatory components of the HPA axis from glucocorticoid-induced deterioration.