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Open AccessArticle

Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study

1
Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 146 rue Léo Saignat, B.P.281, F-33000 Bordeaux CEDEX, France
2
Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Institute for Research and Innovation in Biomedicine of Normandy (IRIB), Normandie Univ, UNIROUEN, INSERM, U1239, CHU Rouen, 76000 Rouen, France
3
Department of Medical Biochemistry, Rouen University Hospital, 76000 Rouen, France
4
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta
5
Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AT, UK
6
Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, SS 554, km 4,500, 09042 Monserrato, Cagliari, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(12), 2925; https://doi.org/10.3390/ijms20122925
Received: 22 May 2019 / Revised: 9 June 2019 / Accepted: 12 June 2019 / Published: 14 June 2019
(This article belongs to the Special Issue Serotonin in Health and Disease)
The effects triggered by serotonin2C (5-hydroxytryptamin2C, 5-HT2C) receptor agonists in the brain are often subtle, and methodologies highlighting their widespread actions to account for their multiple modulatory influences on behaviors are still lacking. We report an extended analysis of a neurochemical database on monoamines obtained after the intraperitoneal administration of the preferential 5-HT2C receptor agonist WAY-163909 (0.3 and 3 mg/kg) in 29 distinct rat brain regions. We focused on the metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), the metabolites of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the index of the turnovers 5-HIAA/5-HT and DOPAC/DA. WAY-163909 increased and decreased 5-HIAA tissue levels in the amygdala and dorsolateral orbitofrontal cortex, respectively, and decreased the 5-HT turnover in the infralimbic cortex. It enhanced HVA levels in the medial orbitofrontal cortex and DOPAC levels in the amygdala. WAY-163909 increased and decreased DA turnover in the medial orbitofrontal cortex and the anterior insular cortex, respectively. The correlative analysis of the turnovers between pairs of brain regions revealed low levels of correlations across the brain but presented a distinct pattern of correlations after WAY-163909 was compared to saline-treated rats. WAY-163909, notably at 0.3 mg/kg, favored cortico-cortical and cortico-subcortical correlations of both turnovers separately, and frontal DOPAC/DA ratio with cortical and subcortical 5-HIAA/5-HT ratios at 3 mg/kg. In conclusion, the qualitative, but not the quantitative analysis shows that WAY-163909 alters the pattern of correlations across the brain, which could account for its multiple behavioral influences. View Full-Text
Keywords: metabolism; dopamine; serotonin; 5-HIAA; HPLC; HVA; DOPAC; correlative analysis; 5-HT2C receptor; connectivity metabolism; dopamine; serotonin; 5-HIAA; HPLC; HVA; DOPAC; correlative analysis; 5-HT2C receptor; connectivity
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Whitestone, S.; De Deurwaerdère, P.; Baassiri, L.; Manem, J.; Anouar, Y.; Di Giovanni, G.; Bharatiya, R.; Chagraoui, A. Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study. Int. J. Mol. Sci. 2019, 20, 2925.

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