The corticosterone-enhancing effects of the 5-HT1A receptor antagonist, (S)-UH301, are not mediated by the 5-HT1A receptor.
We tried to antagonize the endocrine and behavioural changes induced by the selective 5-HT1A receptor agonist, flesinoxan, with the putative 5-HT1A receptor antagonist, (S)-UH301 ((S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin). The interaction of (S)-UH301 (3 and 10 mg/kg s.c.) with flesinoxan (3 mg/kg s.c.) showed no antagonistic effects of (S)-UH301 on flesinoxan-induced corticosterone secretion. In fact, like flesinoxan (1 and 3 mg/kg s.c.), (S)-UH301 (3 and 10 mg/kg s.c.) itself dose dependently increased plasma corticosterone levels. Unlike flesinoxan, (S)-UH301 did not induce hyperglycemia, lower lip retraction and flat body posture. Moreover, flesinoxan-induced hyperglycemia and behavioural changes were effectively antagonized by (S)-UH301, showing potent 5-HT1A receptor antagonistic effects of (S)-UH301. Therefore we conclude that (S)-UH301 is a potent 5-HT1A receptor antagonist and that the (S)-UH301-induced corticosterone secretion is mediated by a non-5-HT1A receptor mechanism.
Groenink
L
L
Department of Psychopharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Netherlands.
Van der Gugten
J
J
Mos
J
J
Maes
R A
RA
Olivier
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D003345:Corticosterone / Q000097:blood*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D001786:Blood Glucose; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C064282:UH 301; C056895:flesinoxan; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone