Bisphenol A causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity.
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.
Ishido
Masami
M
Endocrine Disruptors and Dioxin Research Projects, National Institute for Environmental Studies, Tsukuba, Japan. ishido@nies.go.jp
Masuo
Yoshinori
Y
Kunimoto
Manabu
M
Oka
Syuichi
S
Morita
Masatoshi
M
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
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