Review: D1 dopamine receptor—the search for a function: A critical evaluation of the D1/D2 dopamine receptor classification and its functional implications
Abstract
The present review focuses on the hypothesized D1/D2 dopamine (DA) receptor classification, originally based on the form of receptor coupling to adenylate cyclase activity. The pharmacological effects of compounds exhibiting putative selective agonist or antagonist profiles at those DA receptors positively coupled to adenylate cyclase activity (D1 DA receptors) are extensively reviewed. Comparisons are made with the effects of putative selective D2 DA receptor agonists and antagonists, and on the basis of this work, the DA receptor classification is critically evaluated. A variety of biochemical, behavioral, and electrophysiological evidence is presented which supports the view that D1 and D2 DA receptors can interact in both an opposing and synergistic fashion. Particular attention is focused on the possibility that D1 receptor stimulation is required to enable the expression of certain D2 receptor‐mediated effects, and the functional consequences of this form of interaction are considered. A hypothetical model is presented which considers how both the opposing and enabling forms of interaction between D1 and D2 DA receptos can control behavioral expression. Finally, the clinical relevance of this work is discussed and the potential use of selective D1 receptor agonists and antagonists in the treatment of psychotic states and Parkinson's disease is considered.
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The post-synaptic effects of dopaminergic projections from the ventral tegmental area and substantia nigra vary across target regions due to the complex role of receptors such as D1 and D2.
“The post-synaptic effects of dopaminergic projections from the ventral tegmental area and substantia nigra varies across target regions (e.g., different portions of basal ganglia and cortex), due, for instance to the complex role of receptors such as D1 and D2 (Clark and White, 1987).”
From Active Inference, homeostatic regulation and adaptive behavioural control (2015) · cites this paper as Clark and White, 1987
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- Authors
- Clark, D., & White, F. J.
- Affiliations
- University of Reading (GB)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- White, Francis J.
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 1987-01
- Volume
- 1
- Issue
- 4
- Pages
- 347-388
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- OpenAlex
- W2010299478
- Cited by
- 660
- References
- 1
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 2 · 2013: 2 · 2012: 9
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH-40832)
- National Institute on Drug Abuse (DA-04093)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine D1 receptor, dopamine D2 receptor, receptor agonists and antagonists, behavioral expression, psychosis, Parkinson's disease
- MeSH terms
- Adenylyl Cyclases, Animals, Benzazepines, Brain, Humans, Receptors, Dopamine, Stereotyped Behavior, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Receptors, Dopamine D1, Receptors, Dopamine D2, Rats
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