Neurochemical impact of the 5-HT 2C receptor agonist WAY-163909 on monoamine tissue content in the rat brain

Serotonin2C receptor (5-HT ) agonists are promising drugs for the treatment of neuropsychiatric diseases. However, their effect is not completely understood in part because they possibly affect several neurobiological networks simultaneously. We studied the effect of the 5-HT receptor agonist WAY-16...

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Veröffentlicht in:Neurochemistry international 2019-03, Vol.124, p.245
Hauptverfasser: Chagraoui, Abdeslam, Whitestone, Sara, Baassiri, Lynn, Manem, Julien, Di Giovanni, Giuseppe, De Deurwaerdère, Philippe
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container_title Neurochemistry international
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creator Chagraoui, Abdeslam
Whitestone, Sara
Baassiri, Lynn
Manem, Julien
Di Giovanni, Giuseppe
De Deurwaerdère, Philippe
description Serotonin2C receptor (5-HT ) agonists are promising drugs for the treatment of neuropsychiatric diseases. However, their effect is not completely understood in part because they possibly affect several neurobiological networks simultaneously. We studied the effect of the 5-HT receptor agonist WAY-163909 (0.3 and 3 mg/kg; i.p.) on the tissue concentration of dopamine (DA), 5-HT and noradrenaline (NA) in 29 rat brain regions related to motor, cognitive, mood and vegetative networks. We found that WAY-163909, without altering the tissue concentration of NA, increased 5-HT concentrations in the medial orbitofrontal cortex and the motor cortex M2 at 3 mg/kg and decreased it in the dorsolateral orbitofrontal cortex at 0.3 mg/kg. WAY-163909 enhanced DA concentrations in the central nucleus of the amygdala at 0.3 mg/kg and reduced it in the dorsal hypothalamus at 3 mg/kg. Using correlative analysis of the tissue content of monoamines, WAY-163909 dramatically changed the profile and the pattern of the correlations within and between monoaminergic systems without drastically changing the total number of these correlations. The profile of these changes in correlations was dose-dependent as it was very different between the two doses within and among monoaminergic systems. In conclusion, the data indicated that the 5-HT receptor agonist WAY-163909 quantitatively alters monoamine content in very few regions but promotes multiple changes of monoaminergic connectivity in the brain.
doi_str_mv 10.1016/j.neuint.2019.01.019
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Using correlative analysis of the tissue content of monoamines, WAY-163909 dramatically changed the profile and the pattern of the correlations within and between monoaminergic systems without drastically changing the total number of these correlations. The profile of these changes in correlations was dose-dependent as it was very different between the two doses within and among monoaminergic systems. 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subjects Animals
Azepines - pharmacology
Biogenic Monoamines - agonists
Biogenic Monoamines - antagonists & inhibitors
Biogenic Monoamines - metabolism
Brain - drug effects
Brain - metabolism
Indoles - pharmacology
Male
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT2C - metabolism
Serotonin 5-HT2 Receptor Agonists - pharmacology
title Neurochemical impact of the 5-HT 2C receptor agonist WAY-163909 on monoamine tissue content in the rat brain
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