FLESINOXAN DOSE-DEPENDENTLY REDUCES EXTRACELLULAR 5-HYDROXYTRYPTAMINE(5-HT) IN RAT MEDIAN RAPHE AND DORSAL HIPPOCAMPUS THROUGH ACTIVATION OF 5-HT1A RECEPTORS

The effects of systemic administration of the serotonin (5-hydroxytryp tamine) 5-HT1A receptor agonists flesinoxan and 8-hydroxy-2-(di-n-prop ylamino)tetralin on extracellular 5-HT were measured using microdialys is probes in both median raphe nucleus and dorsal hippocampus. Both 5- HT1A agonists dose-dependently decreased dialysate 5-HT levels from bo th brain regions. The effects of flesinoxan in the median raphe (0.3 m g/ kg) and dorsal hippocampus (1.0 mg/kg) could be blocked by the 5-HT ,A receptor antagonist nyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohex ane carboxamide trihydrochloride (WAY 100,635) at a dose of 0.05 mg/kg s.c. The antagonist itself had no effect at this dosage. Local perfus ion of flesinoxan for 30 min through the dialysis probe into the media n raphe region at concentrations of 20, 100, and 1,000 mM resulted in a significant decrease in dialysate 5-HT content from both regions. Th e effect of 100 nM flesinoxan could be blocked by coperfusion of 1,000 nM WAY 100,635. The data indicate that flesinoxan is a potent 5-HT1A receptor agonist and also support the notion that somatodendritic 5-HT 1A autoreceptors regulate both terminal and somatodendritic 5-HT relea se.