New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD.
Abstract
Attention deficit hyperactivity disorder (ADHD) is a common childhood psychiatric condition that is effectively treated by catecholaminergic drugs with a variety of different mechanisms and the SH rat is frequently used as a model of this disorder. In vivo microdialysis in freely-moving rats has been employed extensively to provide a better understanding of the pharmacodynamics of drugs at their sites of action. In this review, these three topics are brought together to explore the contribution of in vivo microdialysis studies in spontaneously hypertensive (SH) rats to our understanding of the neurochemical deficits in this rat strain and the actions of ADHD drugs on catecholaminergic function in the prefrontocortex (PFC), striatum and nucleus accumbens. What is revealed is that basal efflux of norepinephrine in the PFC is attenuated, whilst striatal and mesolimbic dopaminergic neurotransmission is hyperfunctional; the latter observation fits closely with the hyperactive phenotype of the SH rat. Furthermore, experiments performed with the enantiomers of amphetamine and threo-methylphenidate demonstrate that pharmacodynamic effects of drugs reported from experiments in outbred rat strains, e.g. Sprague-Dawleys, do not necessarily translate to the SH rat. When the findings are compared with the clinical efficacy of drugs used in treating ADHD, they indicate that the most efficacious drugs powerfully increase both norepinephrinergic and dopaminergic neurotransmission.
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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 Heal et al., 2008
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BackgroundTHE BEHAVIOR OF CHILDREN RECEIVING BENZEDRINE
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The neuropharmacology of ADHD drugs in vivo: Insights on efficacy and safety
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The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD
Natsheh, J. Y., & Shiflett, M. W. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00326 · Cited by 21 · see citing works
Palm, D., Uzoni, A., Simon, F., Fischer, M., Coogan, A., Tucha, O., Thome, J., & Faltraco, F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.007 · Cited by 20 · see citing works
- Authors
- Heal, D. J., Smith, S. L., Kulkarni, R. S., & Rowley, H. L.
- Affiliations
- RenaSci (United Kingdom) (GB)
- Corresponding author
- Heal, D.J.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 90
- Issue
- 2
- Pages
- 184-197
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2122833692
- Cited by
- 105
- References
- 11
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 13 · 2014: 11 · 2013: 10 · 2012: 13
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shire
- National Institutes of Health
- National Institute of Mental Health
- 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, in vivo microdialysis, pharmacodynamics, norepinephrine efflux, striatum, nucleus accumbens, dopamine signaling, hyperactivity, animal model of ADHD
- MeSH terms
- Atomoxetine Hydrochloride, Amphetamine, Animals, Attention Deficit Disorder with Hyperactivity, Disease Models, Animal, Dopamine, Humans, Methylphenidate, Norepinephrine, Propylamines, Rats, Inbred SHR, Rats, Inbred WKY, Microdialysis, Rats
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