Locomotor hyperactivity following prenatal exposure to 5-bromo-2′-deoxyuridine: neurochemical and behavioral evidence of dopaminergic and serotonergic alterations

• DOI: 10.1016/j.toxlet.2004.03.019
• Publication Date: 2004-05-08T08:09:36Z
• Authors: Makiko Kuwagata; Katsumasa T Muneoka; Tetsuo Ogawa; Morikuni Takigawa; Tetsuji Nagao
• Keywords: Male; Antimetabolites, Antineoplastic; 0303 health sciences; Receptors, Dopamine D2; Motor Activity; Rats; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Bromodeoxyuridine; Attention Deficit Disorder with Hyperactivity; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Serotonin; Animals; Dopamine Antagonists; Female

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.