Effects of neonatal treatment with 6-hydroxydopamine and endocrine disruptors on motor activity and gene expression in rats.

Abstract

To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 microg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age. In the midbrain, gene expression was enhanced in dopamine transporter 1; a platelet-derived growth factor receptor; dopamine receptor D4; galanin receptor 2; arginine vasopressin receptor 2; neuropeptide Y; tachykinin 2; and fibroblast growth factor 10. Expression was also enhanced in the glutamate/aspartate transporter gene in the striatum. Rats received an endocrine disruptor (87 nmol), such as bisphenol A, nonylphenol, p-octylphenol, or diethylhexylphthalate, which also caused motor hyperactivity at 4 weeks. The effects of bisphenol A on motor activity were dose-dependent from 0.87 to 87 nmol. The phenols caused a deficit in dopamine neurons, similarly to the deficit caused by 6-hydroxydopamine. Gene-expression profiles after treatment with endocrine disruptors showed variation and differed from those of 6-hydroxydopamine. The results suggest that neonatal treatment with environmental chemicals can generate an animal model of attention-deficit hyperactivity disorder, in which clinical symptoms are pervasive.

• Authors: Yoshinori Masuo, Masami Ishido, Masatoshi Morita, Syuichi Oka
• Journal: Neural plasticity (Neural Plast) Vol. 11 Issue 1-2 Pg. 59-76 ( 2004) ISSN: 2090-5904 [Print] United States
• PMID: 15303306 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Estrogens, Non-Steroidal
• Phenols
• Oxidopamine
• Diethylhexyl Phthalate
• bisphenol A

Topics

• Animals
• Animals, Newborn
• Attention Deficit Disorder with Hyperactivity (chemically induced, metabolism)
• Benzhydryl Compounds
• Brain (drug effects, metabolism)
• Diethylhexyl Phthalate (pharmacology, toxicity)
• Dose-Response Relationship, Drug
• Estrogens, Non-Steroidal (pharmacology, toxicity)
• Female
• Gene Expression Regulation, Developmental (drug effects, physiology)
• Male
• Motor Activity (drug effects, genetics, physiology)
• Oxidopamine (pharmacology)
• Phenols (pharmacology)
• Pregnancy
• Rats
• Rats, Wistar