title: Exposure to methamidophos at adulthood adversely affects serotonergic biomarkers in the mouse brain.
abstract: Epidemiologic studies describe a potential risk of depression and suicide in farm workers exposed to organophosphates (OPs). In a previous study we observed an increase in depressive-like behavior in adult mice exposed to the OP pesticide methamidophos. Considering the association between depression and the serotonergic (5HT) system, in the present study we investigated whether a subchronic exposure to methamidophos affects the serotonergic system of adult mice. From postnatal day 60 to 89 (PN60 to PN89), one of two concentrations of methamidophos (higher dose: 5.25 μg/ml; lower dose: 1.31 μg/ml) or vehicle was administered in the drinking water of male Swiss mice. We evaluated three serotonergic biomarkers during (PN89) and after (PN100) the exposure period: 5HT(1A) receptor binding with [(3)H]OH-DPAT, 5HT(2) receptor binding with [(3)H]ketanserin and 5HT transporter binding with [(3)H]paroxetine. Methamidophos elicited robust decreases in binding for all 5HT markers. These decreases were evident in brain regions containing 5HT cell bodies and dendritic arbors (midbrain, brainstem) as well as in the cerebral cortex, which contains 5HT projections. In the cerebral cortex, effects were identified in mice exposed to the higher dose of methamidophos while in the midbrain and brainstem, both doses elicited significant effects. Overall, effects were present both during and after exposure, even though there were some regional disparities regarding the persistence of effects. Our results indicate that exposure to methamidophos affects synaptic transmission promoting decreases of specific serotonergic biomarkers. These data suggest a mechanism of action of this pesticide that might explain the increased depressive-like behavior in adult mice.
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. Prof. Manoel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ 20550-170, Brazil.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Lima
authors.forename: André L
authors.initials: AL
authors.lastname: Nunes-Freitas
authors.forename: Anderson
authors.initials: A
authors.lastname: Ribeiro-Carvalho
authors.forename: Cláudio C
authors.initials: CC
authors.lastname: Filgueiras
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.forename: Armando
authors.initials: A
authors.lastname: Meyer
authors.forename: Yael
authors.initials: Y
authors.lastname: Abreu-Villaça
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000139:chemically induced / Q000378:metabolism; D015536:Down-Regulation; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D007306:Insecticides; D009946:Organothiophosphorus Compounds; D044348:Receptors, Serotonin, 5-HT2; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C014655:methamidophos