title: Gestational exposure to perfluorooctanoic acid (PFOA): Alterations in motor related behaviors.
abstract: Perfluoroalkyl and polyfluoroalkyl substances are used in commercial applications and developmental exposure has been implicated in alterations in neurobehavioral functioning. While associations between developmental perfluorooctanoic acid (PFOA) exposure and human outcomes have been inconsistent, studies in experimental animals suggest alterations in motor related behaviors. To examine a dose-response pattern of neurobehavioral effects following gestational exposure to PFOA, pregnant CD-1 mice received PFOA (0, 0.1, 0.3, 1.0mg/kg/day) via oral gavage from gestational day 1-17 and the male offspring examined. Motor activity assessments on postnatal day (PND)18, 19, and 20 indicated a shift in the developmental pattern with an elevated activity level observed in the 1.0mg/kg/day dose group on PND18. In the adult, no alterations were observed in body weights, activity levels, diurnal pattern of running wheel activity, startle response, or pre-pulse startle inhibition. In response to a subcutaneous injection of saline or nicotine (80μg/kg), all animals displayed a transient increase in activity likely associated with handling with no differences observed across dose groups. Inhibition of motor activity over 18days of 400μg/kg nicotine injection was not significantly different across dose groups. Hyperactivity induced by 2mg/kg (+)-methamphetamine hydrochloride intraperitoneal injection was significantly lower in the 1.0mg/kg/day PFOA dose group as compared to controls. Taken together, these data suggest that the effects on motor-related behaviors with gestational PFOA exposure do not mimic those reported for acute postnatal exposure. Changes were not observed at dose levels under 1.0mg/kg/day PFOA. Further examination of pathways associated with methamphetamine-induced activity is warranted.
authors.affiliation: Comparative Medicine Branch, Division of Intramural Research; National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Goulding
authors.affiliation: Reproductive Endocrinology Group, National Toxicology Program Laboratory (NTPL), Division of the National Toxicology Program (DNTP), NIEHS, USA.
authors.forename: Sally S
authors.initials: SS
authors.lastname: White
authors.affiliation: Social & Scientific Systems, Inc., Durham, NC 2770, USA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: McBride
authors.affiliation: Reproductive Endocrinology Group, National Toxicology Program Laboratory (NTPL), Division of the National Toxicology Program (DNTP), NIEHS, USA.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Fenton
authors.affiliation: Neurotoxicology Group, NTPL, DNTP, NIEHS, USA. Electronic address: harry@niehs.nih.gov.
authors.forename: G Jean
authors.initials: GJ
authors.lastname: Harry
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000633:toxicity*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D005865:Gestational Age; D051379:Mice; D000068079:Motor Disorders / Q000209:etiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D013216:Reflex, Startle / Q000187:drug effects; D012420:Running
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D018722:Nicotinic Agonists; D009538:Nicotine; C023036:perfluorooctanoic acid
keywords: Amphetamine; Development; Motor activity; Neurotoxicity; Nicotine; Novel environment