Behavioural and biochemical evidence that glucocorticoids are not involved in DOI-elicited 5-HT2 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 beforehand) did not affect either frontal cortex [3H]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 Bmax for [3H]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.
Chaouloff
F
F
Laboratoire de Pharmacologie, Groupe de Neuropharmacologie, CNRS, CHU Necker, Paris, France.
Baudrie
V
V
Coupry
I
I
D000315:Adrenalectomy; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D005938:Glucocorticoids; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine