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Article

Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain

1
Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09100 Cagliari, Italy
2
Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 146 rue Léo Saignat, B.P.281, F-33000 Bordeaux CEDEX, France
3
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
4
Department of Medical Biochemistry, Rouen University Hospital, 76000 Rouen, France
5
Centre of Excellence for the Neurobiology of Addictions, University of Cagliari, 09100 Cagliari, Italy
6
Institute of Neuroscience, National Research Council, Cagliari Section, University of Cagliari, 09100 Cagliari, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(16), 5711; https://doi.org/10.3390/ijms21165711
Received: 25 July 2020 / Revised: 6 August 2020 / Accepted: 6 August 2020 / Published: 9 August 2020
Fipronil (FPN), a widely used pesticide for agricultural and non-agricultural pest control, is possibly neurotoxic for mammals. Brain monoaminergic systems, involved in virtually all brain functions, have been shown to be sensitive to numerous pesticides. Here, we addressed the hypothesis that chronic exposure to FPN could modify brain monoamine neurochemistry. FPN (10 mg/kg) was chronically administered for 21 days through oral gavage in rats. Thereafter, the tissue concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA); and noradrenaline (NA) were measured in 30 distinct brain regions. FPN significantly decreased DA and its metabolite levels in most striatal territories, including the nucleus accumbens and the substantia nigra (SN). FPN also diminished 5-HT levels in some striatal regions and the SN. The indirect index of the turnovers, DOPAC/DA and 5-HIAA/5-HT ratios, was increased in numerous brain regions. FPN reduced the NA content only in the nucleus accumbens core. Using the Bravais–Pearson test to study the neurochemical organization of monoamines through multiple correlative analyses across the brain, we found fewer correlations for NA, DOPAC/DA, and 5-HIAA/5-HT ratios, and an altered pattern of correlations within and between monoamine systems. We therefore conclude that the chronic administration of FPN in rats induces massive and inhomogeneous changes in the DA and 5-HT systems in the brain. View Full-Text
Keywords: pesticide; dopamine; serotonin; nigrostriatal; metabolism; high pressure liquid chromatography pesticide; dopamine; serotonin; nigrostriatal; metabolism; high pressure liquid chromatography
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MDPI and ACS Style

Bharatiya, R.; Chagraoui, A.; De Deurwaerdere, S.; Argiolas, A.; Melis, M.R.; Sanna, F.; De Deurwaerdere, P. Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain. Int. J. Mol. Sci. 2020, 21, 5711. https://doi.org/10.3390/ijms21165711

AMA Style

Bharatiya R, Chagraoui A, De Deurwaerdere S, Argiolas A, Melis MR, Sanna F, De Deurwaerdere P. Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain. International Journal of Molecular Sciences. 2020; 21(16):5711. https://doi.org/10.3390/ijms21165711

Chicago/Turabian Style

Bharatiya, Rahul, Abdeslam Chagraoui, Salomé De Deurwaerdere, Antonio Argiolas, Maria R. Melis, Fabrizio Sanna, and Philippe De Deurwaerdere. 2020. "Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain" International Journal of Molecular Sciences 21, no. 16: 5711. https://doi.org/10.3390/ijms21165711

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