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

Toxicol Lett. 2004 Aug 30;152(1):63-71. doi: 10.1016/j.toxlet.2004.03.019.

Abstract

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.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity*
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Bromodeoxyuridine / toxicity*
  • Disease Models, Animal
  • Dopamine Antagonists / pharmacology
  • Female
  • Male
  • Motor Activity / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / physiology*
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology*

Substances

  • Antimetabolites, Antineoplastic
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Bromodeoxyuridine