ANTAGONISM OF SEROTONIN 5-HT1A RECEPTORS POTENTIATES THE INCREASES INEXTRACELLULAR MONOAMINES INDUCED BY DULOXETINE IN RAT HYPOTHALAMUS

In the current study we examined the effects of coadministration of a serotonin 5-HT1A antagonist, -(1H-indol-4-yloxy)-3-(cyclohexylamino)-2 -propanol maleate (LY 206130), and a dual 5-HT and norepinephrine (NE) uptake inhibitor, duloxetine, on extracellular levels of NE, 5-HT, do pamine (DA), 5-hydroxyindoleacetic acid, and 3,4-dihydroxyphenylacetic acid in rat hypothalamus microdialysates. LY 206130 (3.0 mg/kg, s.c.) alone significantly increased NE and DA levels by 60 and 34%, respect ively, without affecting 5-HT levels. Duloxetine administration at 4.0 mg/kg, i.p. alone produced no significant changes in levels of 5-HT, NE, or DA. In contrast, when LY 206130 and duloxetine were coadministe red at 3.0 mg/kg, s.c. and 4.0 mg/kg, i,p,, respectively, 5-HT, NE, an d DA levels increased to 5.7-, 4.8-, and threefold over their respecti ve basal levels. These data demonstrate that antagonism of somatodendr itic 5-HT1A autoreceptors and concomitant inhibition of 5-HT and NE up -take with duloxetine may promote synergistic increases in levels of e xtracellular 5-HT, NE, and DA in hypothalamus of conscious, freely mov ing rats.