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Antagonism of Serotonin 5‐HT 1A Receptors Potentiates the Increases in Extracellular Monoamines Induced by Duloxetine in Rat Hypothalamus
Author(s) -
Engleman Eric A.,
Robertson David W.,
Thompson Dennis C.,
Perry Kenneth W.,
Wong David T.
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.1471-4159.1996.66020599.x
Subject(s) - serotonin , endocrinology , medicine , duloxetine , chemistry , monoamine neurotransmitter , hypothalamus , microdialysis , antagonist , antagonism , 5 ht receptor , dopamine , extracellular , autoreceptor , serotonergic , receptor antagonist , p chloroamphetamine , pharmacology , receptor , biology , biochemistry , alternative medicine , pathology
In the current study we examined the effects of coadministration of a serotonin 5‐HT 1A antagonist, (±)‐1‐(1 H ‐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‐HT 1A 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.