title: Persistent behavioral alterations in rats neonatally exposed to low doses of the organophosphate pesticide, parathion.
abstract: Although developmental exposures of rats to low levels of the organophosphate pesticides (OPs), chlorpyrifos (CPF) or diazinon (DZN), both cause persistent neurobehavioral effects, there are important differences in their neurotoxicity. The current study extended investigation to parathion (PTN), an OP that has higher systemic toxicity than either CPF or DZN. We gave PTN on postnatal days (PND) 1-4 at doses spanning the threshold for systemic toxicity (0, 0.1 or 0.2 mg/kg/day, s.c.) and performed a battery of emotional and cognitive behavioral tests in adolescence through adulthood. The higher PTN dose increased time spent on the open arms and the number of center crossings in the plus maze, indicating greater risk-taking and overall activity. This group also showed a decrease in tactile startle response without altering prepulse inhibition, indicating a blunted acute sensorimotor reaction without alteration in sensorimotor plasticity. T-maze spontaneous alternation, novelty-suppressed feeding, preference for sweetened chocolate milk, and locomotor activity were not significantly affected by neonatal PTN exposure. During radial-arm maze acquisition, rats given the lower PTN dose committed fewer errors compared to controls and displayed lower sensitivity to the amnestic effects of the NMDA receptor blocker, dizocilpine. No PTN effects were observed with regard to the sensitivity to blockade of muscarinic and nicotinic cholinergic receptors, or serotonin 5HT(2) receptors. This study shows that neonatal PTN exposure evokes long-term changes in behavior, but the effects are less severe, and in some incidences opposite in nature, to those seen earlier for CPF or DZN, findings consistent with our neurochemical studies showing different patterns of effects and less neurotoxic damage with PTN. Our results reinforce the conclusion that low dose exposure to different OPs can have quite different neurotoxic effects, obviously unconnected to their shared property as cholinesterase inhibitors.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Box #3412, Duke University Medical Center, Durham, NC 27710, USA. timofeev@duke.edu
authors.forename: Olga A
authors.initials: OA
authors.lastname: Timofeeva
authors.forename: David
authors.initials: D
authors.lastname: Sanders
authors.forename: Kristen
authors.initials: K
authors.lastname: Seemann
authors.forename: Liwei
authors.initials: L
authors.lastname: Yang
authors.forename: Daniel
authors.initials: D
authors.lastname: Hermanson
authors.forename: Sam
authors.initials: S
authors.lastname: Regenbogen
authors.forename: Samantha
authors.initials: S
authors.lastname: Agoos
authors.forename: Anita
authors.initials: A
authors.lastname: Kallepalli
authors.forename: Anit
authors.initials: A
authors.lastname: Rastogi
authors.forename: David
authors.initials: D
authors.lastname: Braddy
authors.forename: Corinne
authors.initials: C
authors.lastname: Wells
authors.forename: Charles
authors.initials: C
authors.lastname: Perraut
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Seidler
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D007279:Injections, Subcutaneous; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000503:physiopathology*; D010278:Parathion / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007306:Insecticides; D018727:Muscarinic Antagonists; D010278:Parathion; D016291:Dizocilpine Maleate; D012601:Scopolamine