Fluoxetine reduces inflammatory edema in the rat: involvement of the pituitary-adrenal axis.
The acute effect of the non-tricyclic, pro-serotoninergic, antidepressant drug fluoxetine on inflammatory edema was evaluated in the rat. Fluoxetine significantly and dose dependently reduced the swelling induced by the injection of 10% brewer's yeast suspension in the hindpaw. Both adrenalectomy and hypophysectomy prevented the effect of fluoxetine. In contrast pretreatment with the corticotropin-releasing hormone antagonist alpha-helical CRH-(9-41) did not interfere with the anti-inflammatory action of fluoxetine. Moreover, the drug induced a significant increase of corticosterone plasma concentrations in vivo, whereas, in vitro, it did not stimulate beta-endorphin release from anterior pituitary cells. Our data suggest that fluoxetine exerts a potent anti-inflammatory action by inducing pituitary-adrenocortical activation via serotonin.
Bianchi
M
M
Department of Pharmacology, School of Medicine, University of Milano, Italy.
Sacerdote
P
P
Panerai
A E
AE
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy*; D005473:Fluoxetine / Q000627:therapeutic use*; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000378:metabolism
D005473:Fluoxetine; D001615:beta-Endorphin; D003345:Corticosterone