Altered dopaminergic function in the prefrontal cortex, nucleus accumbens and caudate-putamen of an animal model of attention-deficit hyperactivity disorder–the spontaneously hypertensive rat.
Abstract
The spontaneously hypertensive rat (SHR) has been proposed as an animal model for Attention-Deficit Hyperactivity Disorder (ADHD). The behavioural problems of ADHD have been suggested to be secondary to altered reinforcement mechanisms resulting from dysfunction of the mesolimbic and mesocortical dopaminergic systems. The present study therefore investigated whether there are regional differences in dopamine (DA) and acetylcholine (ACh) release and DA D2-receptor function in SHR compared to their normotensive Wistar-Kyoto (WKY) controls. The DA D2-receptor agonist, quinpirole, caused significantly greater inhibition of DA release from caudate-putamen but not from nucleus accumbens or prefrontal cortex slices of SHR relative to WKY. DA D2-receptor blockade by the antagonist, sulpiride, caused a significantly greater increase in DA release from nucleus accumbens slices of SHR compared to WKY suggesting increased efficacy of DA autoreceptors at low endogenous agonist concentrations in the nucleus accumbens of SHR. The electrically-stimulated release of DA was significantly lower in caudate-putamen and prefrontal cortex slices of SHR than in slices of WKY. This could be attributed to increased autoreceptor-mediated inhibition of DA release in caudate-putamen slices but not in the prefrontal cortex. No difference was observed between SHR and WKY with respect to DA D2-receptor-mediated inhibition of ACh release from caudate-putamen or nucleus accumbens slices, suggesting that posts…
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SHR rats display reduced DA signaling and increased DAT expression, similar to ADHD patients.
“Further, SHR rats display reduced DA signaling and increased DA transporter (DAT) expression, similar to ADHD patients (Russell et al., 1995; Russell, 2003; Heal et al., 2008; Roessner et al., 2010).”
From The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD (2015) · cites this paper as Russell et al., 1995
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- Authors
- Russell, V., de Villiers, A., Sagvolden, T., Lamm, M., & Taljaard, J.
- Affiliations
- Stellenbosch University (ZA)
- University of Oslo (NO)
- Corresponding author
- Russell, Vivienne
- ORCID
- Russell, Vivienne
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1995-04
- Volume
- 676
- Issue
- 2
- Pages
- 343-351
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2111012319
- Cited by
- 200
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 12 · 2014: 8 · 2013: 7 · 2012: 6
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- attention deficit hyperactivity disorder, spontaneously hypertensive rats, dopamine release, acetylcholine release, dopamine D2 receptor, dopamine autoreceptors, quinpirole, sulpiride, caudate-putamen, nucleus accumbens, prefrontal cortex, mesolimbic dopamine system, mesocortical dopamine system, animal model of ADHD
- MeSH terms
- Acetylcholine, Analysis of Variance, Animals, Attention Deficit Disorder with Hyperactivity, Caudate Nucleus, Disease Models, Animal, Dopamine, Hypertension, Male, Nucleus Accumbens, Putamen, Rats, Inbred SHR, Rats, Inbred WKY, Neostriatum, Prefrontal Cortex, Receptors, Dopamine D2, Rats
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