In the current study we examined the effects of coadministration of a serotonin 5-HT 1A antagonist, (±)- (LY 206130), and a dual 5-HT and norepinephrine (NE) uptake inhibitor, duloxetine, on extracellular levels of NE, 5-HT, dopamine (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%, respectively, 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 coadministered at 3.0 mg/kg, s.c. and 4.0 mg/kg, i.p., respectively, 5-HI, NE, and DA levels increased to 5.7-, 4.8-, and threefold over their respective basal levels. Ihese data demonstrate that antagonism of somatodendritic 5-HI1A autoreceptors and concomitant inhibition of 5-HI and NE uptake with duloxetine may promote synergistic increases in levels of extracellular 5-HT, NE, and DA in hypothalamus of conscious, freely moving rats. Key Words: LY 2061 3O-.5-HI1A antagonist-5-HT~Areceptors-Duloxetine-Extracellular monoamines-Hypothalamus.