title: Bisphenol A causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity.
abstract: We examined the effects of bisphenol A, an endocrine disruptor, on rat behavioral and cellular responses. Single intracisternal administration of bisphenol A (0.2-20 microg) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age. Rats were about 1.6-fold more active in the nocturnal phase after administration of both 2 and 20 microg of bisphenol A than were control rats. The response was dose-dependent. Based on DNA macroarray analyses of the midbrain, bisphenol A decreased by more than twofold gene expression levels of the dopamine D4 receptor at 4 weeks of age and the dopamine transporter at 8 weeks of age. Furthermore, bisphenol A decreased by more than twofold gene expression levels of the dopamine D4 receptor at 4 weeks of age and the dopamine transporter at 8 weeks of age. We conclude that bisphenol A affected central dopaminergic system activity, resulting in hyperactivity due most likely to a large reduction of tyrosine hydroxylase activity in the midbrain.
authors.affiliation: Endocrine Disruptors and Dioxin Research Projects, National Institute for Environmental Studies, Tsukuba, Japan. ishido@nies.go.jp
authors.forename: Masami
authors.initials: M
authors.lastname: Ishido
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Masuo
authors.forename: Manabu
authors.initials: M
authors.lastname: Kunimoto
authors.forename: Syuichi
authors.initials: S
authors.lastname: Oka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Morita
mesh_terms: D000367:Age Factors; D000818:Animals; D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage*; D005260:Female; D006948:Hyperkinesis / Q000139:chemically induced* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050638:Receptors, Dopamine D4; D013346:Subarachnoid Space; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D004968:Estrogens, Non-Steroidal; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010636:Phenols; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D014446:Tyrosine 3-Monooxygenase; C493601:Drd4 protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds