Bisphenol A causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity

• Published in: Journal of neuroscience research 2004-05, Vol.76 (3), p.423-433
• Main Authors: Ishido, Masami, Masuo, Yoshinori, Kunimoto, Manabu, Oka, Syuichi, Morita, Masatoshi
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Benzhydryl Compounds; bisphenol A; DNA array; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; endocrine disruptors; Estrogens, Non-Steroidal - administration & dosage; Female; hyperactivity; Hyperkinesis - chemically induced; Hyperkinesis - metabolism; Injections, Intraventricular; Male; Membrane Glycoproteins; Membrane Transport Proteins - drug effects; Membrane Transport Proteins - metabolism; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - metabolism; Phenols - administration & dosage; Rats; Rats, Wistar; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D4; Subarachnoid Space; Tyrosine 3-Monooxygenase - drug effects; Tyrosine 3-Monooxygenase - metabolism; tyrosine hydroxylase
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.20050

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 μg) 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 μg 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. © 2004 Wiley‐Liss, Inc.