Serum corticosterone increases reflect enhanced uptake inhibitor-induced elevation of extracellular 5-hydroxytryptamine in rat hypothalamus.
The increase in extracellular 5-hydroxytryptamine (5-HT) in rat hypothalamus following administration of fluoxetine, a 5-HT-uptake inhibitor, was enhanced by the injection of LY206130(1-[1-H-indol-4-yloxy]-3-[cyclohexylamino]-2-prop ano l maleate), a 5HT1A receptor antagonist, or by L-5-hydroxytryptophan (L-5-HTP), the 5-HT precursor. Elevation of serum corticosterone, measured as a functional output of hypothalamic 5-HT pathways, was greater in rats treated with fluoxetine plus LY206130 or with fluoxetine plus L-5-HTP than in rats treated with the agents alone. Synergism between effects of fluoxetine and L-5HTP has often been reported, but this is the first report of an increased functional effect when a 5-HT1A receptor antagonist is combined with a 5-HT uptake inhibitor to augment the increase in extracellular 5-HT.
Fuller
R W
RW
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Centre, Indianapolis, IN 46285, USA.
Perry
K W
KW
Hemrick-Luecke
S K
SK
Engleman
E
E
D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003514:Cyclohexylamines / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D006916:5-Hydroxytryptophan; D003345:Corticosterone; D003514:Cyclohexylamines; D005473:Fluoxetine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C098407:LY 206130