TY - JOUR T1 - Prenatal Nicotine Exposure Mouse Model Showing Hyperactivity, Reduced Cingulate Cortex Volume, Reduced Dopamine Turnover, and Responsiveness to Oral Methylphenidate Treatment JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9410 LP - 9418 DO - 10.1523/JNEUROSCI.1041-12.2012 VL - 32 IS - 27 AU - Jinmin Zhu AU - Xuan Zhang AU - Yuehang Xu AU - Thomas J. Spencer AU - Joseph Biederman AU - Pradeep G. Bhide Y1 - 2012/07/04 UR - http://www.jneurosci.org/content/32/27/9410.abstract N2 - 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. ER -