Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction
Abstract
Background and rationale Reinstatement of the function of working memory, the cardinal cognitive process essential for human reasoning and judgment, is potentially the most intractable problem for the treatment of schizophrenia. Since deficits in working memory are associated with dopamine dysregulation and altered D(1) receptor signaling within prefrontal cortex, we present the case for targeting novel drug therapies towards enhancing prefrontal D(1) stimulation for the amelioration of the debilitating cognitive deficits in schizophrenia. Objectives This review examines the role of dopamine in regulating cellular and circuit function within prefrontal cortex in order to understand the significance of the dopamine dysregulation found in schizophrenia and related non-human primate models. By revealing the associations among prefrontal neuronal function, dopamine and D(1) signaling, and cognition, we seek to pinpoint the mechanisms by which dopamine modulates working memory processes and how these mechanisms may be exploited to improve cognitive function. Results and conclusions Dopamine deficiency within dorsolateral prefrontal cortex leads to abnormal recruitment of this region by cognitive tasks. Both preclinical and clinical studies have demonstrated a direct relationship between prefrontal dopamine function and the integrity of working memory, suggesting that insufficient D(1) receptor signaling in this region results in cognitive deficits. Moreover, working memory deficit…
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Prefrontal D1R hypoactivity has been associated with cognitive deficits and negative symptoms in animal models.
“prefrontal D1R hypoactivity has been associated with cognitive deficits and negative symptoms in animal models (Goldman-Rakic et al., 2004).”
From The Computational Anatomy of Psychosis (2013) · cites this paper as Goldman-Rakic et al., 2004
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- Authors
- Goldman-Rakic, P., Castner, S., Svensson, T., Siever, L., & Williams, G.
- Affiliations
- Karolinska Institutet (SE)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Psychopharmacology
- Published
- 2004-04-30
- Volume
- 174
- Issue
- 1
- Pages
- 3-16
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W1977138162
- Cited by
- 544
- References
- 11
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 16 · 2021: 18 · 2020: 19 · 2019: 20 · 2018: 24 · 2017: 24 · 2016: 27 · 2015: 26 · 2014: 36 · 2013: 39 · 2012: 37
- FWCI
- 20.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- dopamine D1 receptor, schizophrenia, working memory, cognitive impairment, prefrontal cortex, dopamine dysregulation, D1 receptor agonists, nonhuman primate model, dorsolateral prefrontal cortex, cognitive enhancement
- MeSH terms
- Animals, Cognition Disorders, Disease Models, Animal, Dopamine, Humans, Schizophrenia, Dopamine Agents, Signal Transduction, Prefrontal Cortex, Receptors, Dopamine D1
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