title: Prenatal nicotine exposure mouse model showing hyperactivity, reduced cingulate cortex volume, reduced dopamine turnover, and responsiveness to oral methylphenidate treatment.
abstract: Cigarette smoking, nicotine replacement therapy, and smokeless tobacco use during pregnancy are associated with cognitive disabilities later in life in children exposed prenatally to nicotine. The disabilities include attention deficit hyperactivity disorder (ADHD) and conduct disorder. However, the structural and neurochemical bases of these cognitive deficits remain unclear. Using a mouse model we show that prenatal nicotine exposure produces hyperactivity, selective decreases in cingulate cortical volume, and radial thickness, as well as decreased dopamine turnover in the frontal cortex. The hyperactivity occurs in both male and female offspring and peaks during the "active" or dark phase of the light/dark cycle. These features of the mouse model closely parallel the human ADHD phenotype, whether or not the ADHD is associated with prenatal nicotine exposure. A single oral, but not intraperitoneal, administration of a therapeutic equivalent dose (0.75 mg/kg) of methylphenidate decreases the hyperactivity and increases the dopamine turnover in the frontal cortex of the prenatally nicotine exposed mice, once again paralleling the therapeutic effects of this compound in ADHD subjects. Collectively, our data suggest that the prenatal nicotine exposure mouse model has striking parallels to the ADHD phenotype not only in behavioral, neuroanatomical, and neurochemical features, but also with respect to responsiveness of the behavioral phenotype to methylphenidate treatment. The behavioral, neurochemical, and anatomical biomarkers in the mouse model could be valuable for evaluating new therapies for ADHD and mechanistic investigations into its etiology.
authors: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida 32311, USA.
authors: Jinmin
authors: J
authors: Zhu
authors: Xuan
authors: X
authors: Zhang
authors: Yuehang
authors: Y
authors: Xu
authors: Thomas J
authors: TJ
authors: Spencer
authors: Joseph
authors: J
authors: Biederman
authors: Pradeep G
authors: PG
authors: Bhide
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects
chemical_list: D008774:Methylphenidate; D009538:Nicotine; D004298:Dopamine