4.7 Review

Review of rodent models of attention deficit hyperactivity disorder

Journal

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
Volume 132, Issue -, Pages 621-637

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2021.11.041

Keywords

Attention deficit hyperactivity disorder; ADHD; Neurodevelopment; Rodent models; Polygenic disorders; Environmental influences

Funding

  1. Department of Neurology, Cincinnati Children's Hospital Medical Center
  2. University of Cincinnati Graduate School Dean's Dissertation Completion Fellowship
  3. [R01 ES032270]

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This study reviews the impact of genetic and environmental factors on the development of ADHD. Although there is no perfect rodent model, several models show promise. The genetic models mainly include rats and mice, while environmental factors include alcohol, nicotine, and pollutants. Future research should combine multiple gene knockouts and environmental factors to better understand the pathogenesis of ADHD.
Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8-12 % of children and >4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl cyclase-c KO mice, and latrophilin-3 KO mice and rats. Environmental factors thought to contribute to ADHD include ethanol, nicotine, PCBs, lead (Pb), ionizing irradiation, 6-hydroxydopamine, neonatal hypoxia, some pesticides, and organic pollutants. Model validation criteria are outlined, and current genetic models evaluated against these criteria. Future research should explore induced multiple gene KOs given that ADHD is polygenic and epigenetic contributions. Furthermore, genetic models should be combined with environmental agents to test for interactions.

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