title: Dopamine transporter density and behavioral response to methylphenidate in a hyperlocomotor rat model.
abstract: Rats exposed prenatally to 5-bromo-2'-deoxyuridine (BrdU-rats) display hyperlocomotive activity, making them a possibly useful animal model for the study of attention deficit hyperactivity disorder (ADHD). Using this model, we investigated dopamine transporter (DAT) density and behavioral outcomes in BrdU-rats, some of which were also administered methylphenidate, a psychostimulant that is widely used for the treatment of ADHD. Pregnant rats were exposed to BrdU from gestational day 9 through 15. In male offspring, DAT densities in different regions of the striatum were quantified at three weeks of age. At seven weeks of age, locomotor, rearing and grooming behaviors were evaluated in an open-field setting, with or without methylphenidate treatment (1 mg/kg or 4 mg/kg). The results revealed no significant changes in striatal DAT densities in BrdU-rats compared with controls. Extreme hyperlocomotion of BrdU-rats was detected in the open-field environment, an effect that was exacerbated following treatment with the lower and higher dose of methylphenidate. Such increase in locomotor activity was observed only with the higher dose in control animals. In summary, degeneration of dopaminergic neurons in the terminal field was not detected in juvenile BrdU-rats, although adult animals displayed hyperactive behavior in a mildly stressful environment as well as hypersensitivity to a psychostimulant that facilitates dopaminergic neurotransmission.
authors.affiliation: Department of Anatomy I, Showa University School of Medicine, Tokyo, Japan. kmuneoka@med.showa-u.ac.jp
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Muneoka
authors.forename: Makiko
authors.initials: M
authors.lastname: Kuwagata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwata
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Shirayama
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Morikuni
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001973:Bromodeoxyuridine; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008774:Methylphenidate; D001973:Bromodeoxyuridine