Locomotor hyperactivity following prenatal exposure to 5-bromo-2'-deoxyuridine:

neurochemical and behavioral evidence of dopaminergic and serotonergic alterations.

Kuwagata M, Muneoka KT, Ogawa T, Takigawa M, Nagao T.

Safety Testing Laboratory, Food and Drug Safety Center, Hatano Research Institute, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan.

mkuwagat@iupui.edu

Prenatal exposure to 5-bromo-2'-deoxyuridine (BrdU) has been reported to induce abnormal behaviors in offspring, including marked hyperactivity. In this study, the contribution of the serotonin (5-HT) and dopamine (DA) systems to BrdU-induced developmental neurotoxicity was investigated. Sprague-Dawley rats were treated with BrdU on gestational days 9 through 15 (50mg/kg, i.p.) and male offspring (BrdU-rats) were examined. The BrdU-rats exhibited a 3.5-fold increase in locomotor activity. The dopamine D2 receptor antagonist sulpiride increased locomotor activity in the BrdU-rats, but decreased it in control rats. The BrdU-rats responded to the 5-HT1A receptor antagonist NAN190 much more than the controls. The measurement of monoamines revealed significant decreases in DA, dihydroxyphenylacetic acid, and homovanilic acid, and significant increases in 5-HT and 5-hydroxy-3-indolacetic acid, with a decrease in the 5-HT turnover ratio in the striatum of BrdU-rats. Thus, prenatal exposure to BrdU induced alterations in both the DA and 5-HT systems.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15294348&query_hl=1&itool=pubmed_docsum