Sequence analysis of Drd2, Drd4, and Dat1 in SHR and WKY rat strains
Open accessAbstract
Background: The Spontaneously Hypertensive Rat (SHR) shows a number of behaviours that closely parallel those seen in children with attention-deficit hyperactivity disorder. These include motor hyperactivity, excessive responses under a fixed-interval/extinction schedule, difficulty in acquiring operant tasks and increased sensitivity to immediate behavioural reinforcement. As in children with ADHD, the behavioural and cognitive deficits in the SHR are responsive to stimulants, including d-amphetamine and d,l-methylphenidate. The non-hyperactive Wistar Kyoto (WKY) rat strain is often used as a control in behavioural studies of the SHR, and WKY itself has been suggested to be a useful animal model of depression. Numerous studies have shown that dopaminergic neurotransmission is altered between the two strains. Human genetic studies have found associations between several dopaminergic genes and both ADHD and depression. Methods: We sequenced three candidate dopaminergic genes (Drd2, Drd4, and Dat1) in the SHR and WKY to identify between-strain sequence differences. Results: No between-strain sequence differences were found in either Drd2 or Drd4, but several variations were found in the Dat1 gene that encodes the dopamine transporter. Conclusion: It is plausible that DNA sequence changes in the Dat1 gene account for some of the behavioural differences observed between the SHR and WKY strains. Future work will focus on elucidating the functional effects of the observed polymorphisms.
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The SHR possesses a 160-bp insertion in the noncoding region upstream of exon 3 of the DAT gene.
“The SHR possesses a 160-bp insertion in the noncoding region upstream of exon 3 of the DAT gene [455]”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [455]
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- Authors
- Mill, J., Sagvolden, T., & Asherson, P.
- Affiliations
- King's College London (GB)
- University of Oslo (NO)
- Corresponding author
- Asherson, Philip
- Venue
- Behavioral and Brain Functions
- Published
- 2005-12
- Volume
- 1
- Issue
- 1
- Pages
- 24-24
- ISSN
- 1744-9081 (ISSN-L)
- PMC
- PMC1363350
- OpenAlex
- W2115841882
- Cited by
- 49
- References
- 22
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Behavioral and Brain Functions (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- dopamine D2 receptor, dopamine D4 receptor, dopamine transporter, DAT1, DRD2, DRD4, spontaneously hypertensive rats, Wistar-Kyoto rats, attention deficit hyperactivity disorder, animal models of depression, dopaminergic genes, genetic polymorphism, sequence variation, motor hyperactivity
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