title: Sex-dimorphic effects of gestational exposure to the organophosphate insecticide chlorpyrifos on social investigation in mice.
abstract: Several pieces of evidence from animal and human studies indicate that the organophosphate insecticide chlorpyrifos (CPF) acts as a developmental neurotoxicant at environmentally relevant doses, and it is possibly endowed with endocrine-disrupting activity. Data collected in rodent models show that developmental exposure to CPF at sub-toxic doses induces long-lasting and sex-dimorphic changes in social and investigative responses in exposed offspring. The aim of this study was to evaluate the effects of gestational CPF treatment on social and olfactory discrimination in adult mice of both sexes. Pregnant CD1 out-bred mice were exposed to CPF per os on gestational days (GD) 14-17 at the sub-toxic dose of 6 mg/kg/bw. At adulthood, male and female offspring underwent the same experimental paradigms, namely i) a social discrimination test where mice were presented with a simultaneous binary choice between a novel conspecific and a familiar one, and ii) an olfactory habituation/dishabituation test to evaluate their capability to discriminate between odors with different eco-ethological salience (non-social vs. social odors). Results showed that in the social discrimination test prenatal CPF primarily affected the female sex by raising the investigation time in females to the same levels as found in vehicle- and CPF-exposed males. The ability to discriminate between a familiar and a novel social mate was not affected by CPF in either sex. In the olfactory habituation/dishabituation test, mice of both sexes successfully discriminated non-social from social odors regardless of the prenatal treatment received. These results confirm previous evidence indicating that developmental exposure to CPF causes long-lasting and sex-dimorphic changes in responsiveness to social cues, in the absence of significant impairment of social and olfactory discrimination capacity. These findings are discussed within the framework of recent data pointing to the limbic/hypothalamic circuitry and steroid hormonal regulations as possible targets for CPF neurotoxicity.
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy; Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, I-00161 Rome, Italy. Electronic address: alessiadefelice5@gmail.com.
authors.forename: Alessia
authors.initials: A
authors.lastname: De Felice
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy. Electronic address: aldina.venerosi@iss.it.
authors.forename: Aldina
authors.initials: A
authors.lastname: Venerosi
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy. Electronic address: laura.ricceri@iss.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Ricceri
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy; Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Piazzale Aldo Moro 5, I-00161 Rome, Italy. Electronic address: mara.sabbioni@hotmail.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Sabbioni
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy. Electronic address: marialuisa.scattoni@iss.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Scattoni
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy. Electronic address: flavia.chiarotti@iss.it.
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiarotti
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy. Electronic address: gemma.calamandrei@iss.it.
authors.forename: Gemma
authors.initials: G
authors.lastname: Calamandrei
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004390:Chlorpyrifos / Q000633:toxicity*; D004192:Discrimination, Psychological / Q000187:drug effects; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D009812:Odorants; D055696:Olfactory Perception / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D012737:Sex Factors; D012919:Social Behavior
chemical_list: D007306:Insecticides; D004390:Chlorpyrifos
keywords: Chlorpyrifos; Olfactory discrimination; Rodents; Sex differences; Social discrimination; Social investigation