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Flesinoxan Dose‐Dependently Reduces Extracellular 5‐Hydroxytryptamine (5‐HT) in Rat Median Raphe and Dorsal Hippocampus Through Activation of 5‐HT 1A Receptors
Author(s) -
Bosker Fokko J.,
De Winter Tessa Y. C. E.,
Klompmakers André A.,
Westenberg Herman G. M.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66062546.x
Subject(s) - dorsal raphe nucleus , 5 ht1a receptor , chemistry , raphe nuclei , microdialysis , median raphe nucleus , agonist , medicine , endocrinology , 5 ht receptor , serotonin , receptor antagonist , pharmacology , antagonist , serotonergic , receptor , extracellular , biochemistry
The effects of systemic administration of the serotonin (5‐hydroxytryptamine) 5‐HT 1A receptor agonists flesinoxan and 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin on extracellular 5‐HT were measured using microdialysis probes in both median raphe nucleus and dorsal hippocampus. Both 5‐HT 1A agonists dose‐dependently decreased dialysate 5‐HT levels from both brain regions. The effects of flesinoxan in the median raphe (0.3 mg/kg) and dorsal hippocampus (1.0 mg/kg) could be blocked by the 5‐HT 1A receptor antagonist N ‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐ N ‐(2‐pyridyl)cyclohexane 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 perfusion of flesinoxan for 30 min through the dialysis probe into the median raphe region at concentrations of 20, 100, and 1,000 n M resulted in a significant decrease in dialysate 5‐HT content from both regions. The effect of 100 n M flesinoxan could be blocked by coperfusion of 1,000 n M WAY 100,635. The data indicate that flesinoxan is a potent 5‐HT 1A receptor agonist and also support the notion that somatodendritic 5‐HT 1A autoreceptors regulate both terminal and somatodendritic 5‐HT release.