title: A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).
abstract: Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.
authors: Department of Biological Sciences (A.W.S., A.S.D., H.B.P.), North Carolina State University, and W. M. Keck Center for Behavioral Biology (A.W.S., A.S.D., H.B.P.), Raleigh, North Carolina 27695; and Department of Biology and Integrated Bioscience Program (E.C.B., L.A.S., A.P., B.S.C.), University of Akron, Akron, Ohio 44333.
authors: Alana W
authors: AW
authors: Sullivan
authors: Elsworth C
authors: EC
authors: Beach
authors: Lucas A
authors: LA
authors: Stetzik
authors: Amy
authors: A
authors: Perry
authors: Alyssa S
authors: AS
authors: D'Addezio
authors: Bruce S
authors: BS
authors: Cushing
authors: Heather B
authors: HB
authors: Patisaul
mesh_terms: D000339:Affect / Q000187:drug effects; D000818:Animals; D003411:Arvicolinae / Q000502:physiology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D003674:Defense Mechanisms; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009490:Neurosecretory Systems / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D012919:Social Behavior; D018675:Toxicity Tests; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds