Decreased beta-adrenergic receptors in rat brain after chronic administration of the selective serotonin uptake inhibitor fluoxetine.
Fluoxetine, a novel antidepressant compound that potently and selectively inhibits serotonin uptake, was chronically administered to laboratory rats. Using in vitro receptor autoradiographic techniques, we found that the binding of [3H]-dihydroalprenolol [( 3H]-DHA) decreased significantly in frontal cortex layers. Analysis of saturation experiments indicated that the reduction was due to a change in number but not affinity of [3H]-DHA binding sites. The data support the hypothesis that the mechanism of action of most antidepressant compounds involves a change in beta-adrenergic receptor function.
Byerley
W F
WF
Department of Psychiatry, University of Utah Medical Center, Salt Lake City 84132.
McConnell
E J
EJ
McCabe
R T
RT
Dawson
T M
TM
Grosser
B I
BI
Wamsley
J K
JK
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004082:Dihydroalprenolol; D005473:Fluoxetine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011437:Propylamines; D011943:Receptors, Adrenergic, beta; D005473:Fluoxetine; D004082:Dihydroalprenolol