Antagonism of Serotonin 5‐HT1A Receptors Potentiates the Increases in Extracellular Monoamines Induced by Duloxetine in Rat Hypothalamus
- 1 February 1996
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 66 (2) , 599-603
- https://doi.org/10.1046/j.1471-4159.1996.66020599.x
Abstract
In the current study we examined the effects of coadministration of a serotonin 5-HT1A antagonist, (±)-1-(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, 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-HT, NE, and DA levels increased to 5.7-, 4.8-, and threefold over their respective basal levels. These data demonstrate that antagonism of somatodendritic 5-HT1A autoreceptors and concomitant inhibition of 5-HT 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.Keywords
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