BEHAVIORAL AND BIOCHEMICAL-EVIDENCE THAT GLUCOCORTICOIDS ARE NOT INVOLVED IN DOI-ELICITED 5-HT(2) RECEPTOR DOWN-REGULATION

Numerous studies have brought evidence for reciprocal relationships between glucocorticoids and 5-HT2 receptors; however, whether glucocorticoids affect 5-HT2 receptor regulation is still unknown. Herein, we have analyzed whether 5-HT2 receptor down-regulation following repeated administration of the 5-HT2/5-HT1C receptor agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) is affected by glucocorticoid removal. Compared with sham surgery, adrenalectomy (11-15 days before-hand) did not affect either frontal cortex [H-3]ketanserin binding nor the number of head shakes elicited by a single administration of DOI (2.5 mg/kg s.c.). Pretreatment with DOI (2.5 mg/kg s.c. X 4 in 48 h) decreased to similar extents the head shake response to DOI injection in sham (- 88%) and adrenalectomised (- 95%) rats. Confirmingly, this paradigm was found to diminish the B(max) for [H-3]ketanserin binding in sham and adrenalectomised rats by 64% and 46%, respectively. From these data, it is concluded that glucocorticoid removal does not alter 5-HT2 receptor binding and function nor does it affect 5-HT2 receptor down-regulation.