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Atten Defic Hyperact Disord. 2010 Mar;2(1):21-30. doi: 10.1007/s12402-010-0021-3. Epub 2010 Mar 6.

Strengths and limitations of genetic models of ADHD.

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1
Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genoa, Italy. raul.gainetdinov@iit.it

Abstract

The cause and pathophysiology of attention-deficit hyperactivity disorder (ADHD) are unknown, but compelling evidence suggests an involvement of genetic factors. While dopamine is believed to play a major role in ADHD, the role for norepinephrine and serotonin systems has also been indicated. Mutant mice are valuable tools to dissect the contribution of specific neurotransmitter systems to brain dysfunction and particularly useful to decode complex multi-transmitter interaction that is critical to the pathophysiology of ADHD. Genetically altered mice provided also an opportunity to test experimentally the role of novel candidate genes for this disorder identified in genetic clinical studies. While it is clear that no rodent model would be able to recapitulate fully the complex nature of ADHD, certain endophenotypes could be reasonably well mimicked in these models. Multiple studies have reported associations between polymorphisms in dopamine transporter (DAT) gene and ADHD. Although the functional consequences of these associations are still unclear, it is believed that alterations in DAT-mediated processes might contribute to the pathogenesis of ADHD. Mice lacking the dopamine transporter have elevated dopaminergic tone and represent a genetic animal model in which certain endophenotypes of ADHD can be recapitulated. These mutants as well as other mouse models of DAT dysfunction provided an opportunity to investigate the neuronal circuitry and molecular mechanisms involved in the inhibitory action of psychostimulants on hyperactivity. Several additional knockout and transgenic mouse models have been proposed to model ADHD. Strengths and limitations of currently available genetic mouse models of ADHD are discussed.

PMID:
21432587
DOI:
10.1007/s12402-010-0021-3
[Indexed for MEDLINE]
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