The Role of Dopamine Receptor 3 in Neuropsychiatric Disorders: A Brief Narrative Review

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Hauptverfasser: Guanqing Li, Yanbiao Zhong, Zhangwei Song, Haishui Shi, Xinyu Nan, Zheng Zhu, Yun‐Feng Zhang
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Veröffentlicht: Wiley 2026
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author Guanqing Li
Yanbiao Zhong
Zhangwei Song
Haishui Shi
Xinyu Nan
Zheng Zhu
Yun‐Feng Zhang
author_facet Guanqing Li
Yanbiao Zhong
Zhangwei Song
Haishui Shi
Xinyu Nan
Zheng Zhu
Yun‐Feng Zhang
Guanqing Li
Yanbiao Zhong
Zhangwei Song
Haishui Shi
Xinyu Nan
Zheng Zhu
Yun‐Feng Zhang
collection Wiley Open Access
contents The Role of Dopamine Receptor 3 in Neuropsychiatric Disorders: A Brief Narrative Review Guanqing Li Yanbiao Zhong Zhangwei Song Haishui Shi Xinyu Nan Zheng Zhu Yun‐Feng Zhang Flavour and Fragrance Journal ABSTRACT The dopamine D3 receptor (D3R), a D2‐like family member, is distinguished by its predominant expression within mesolimbic circuitry, including the nucleus accumbens, amygdala, and prefrontal cortex, and its supraphysiological affinity for dopamine, enabling tonic regulation of reward, emotion, and cognition. Beyond canonical Gi/o‐mediated cAMP inhibition, D3R engages diverse signalling cascades (ERK/MAPK, Akt/mTOR, β‐arrestin, CaMKIIα) that orchestrate synaptic plasticity, neuroinflammation, and gene expression in a cell‐type‐ and region‐specific manner. This unique pharmacological and anatomical profile positions D3R as a critical nexus in neuropsychiatric pathophysiology. Critically, emerging clinical evidence suggests that D3R dysregulation, including the D3R Ser9Gly (rs6280) polymorphism, may contribute to individual differences in schizophrenia symptom domains, bipolar disorder mood cycling, treatment‐resistant anxiety, and methylphenidate response variability in ADHD. Unlike pan‐dopaminergic agents, highly selective D3R modulation offers unprecedented therapeutic precision: antagonists ameliorate positive symptoms and cognitive deficits without extrapyramidal side effects, while partial agonists like cariprazine stabilize mood and mitigate anhedonia. These findings collectively underscore D3R as a transformative biomarker and druggable target for next‐generation precision therapeutics in psychiatry. 10.1002/ffj.70113 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/ffj.70113
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spellingShingle The Role of Dopamine Receptor 3 in Neuropsychiatric Disorders: A Brief Narrative Review
Guanqing Li
Yanbiao Zhong
Zhangwei Song
Haishui Shi
Xinyu Nan
Zheng Zhu
Yun‐Feng Zhang
Flavour and Fragrance Journal
The Role of Dopamine Receptor 3 in Neuropsychiatric Disorders: A Brief Narrative Review Guanqing Li Yanbiao Zhong Zhangwei Song Haishui Shi Xinyu Nan Zheng Zhu Yun‐Feng Zhang Flavour and Fragrance Journal ABSTRACT The dopamine D3 receptor (D3R), a D2‐like family member, is distinguished by its predominant expression within mesolimbic circuitry, including the nucleus accumbens, amygdala, and prefrontal cortex, and its supraphysiological affinity for dopamine, enabling tonic regulation of reward, emotion, and cognition. Beyond canonical Gi/o‐mediated cAMP inhibition, D3R engages diverse signalling cascades (ERK/MAPK, Akt/mTOR, β‐arrestin, CaMKIIα) that orchestrate synaptic plasticity, neuroinflammation, and gene expression in a cell‐type‐ and region‐specific manner. This unique pharmacological and anatomical profile positions D3R as a critical nexus in neuropsychiatric pathophysiology. Critically, emerging clinical evidence suggests that D3R dysregulation, including the D3R Ser9Gly (rs6280) polymorphism, may contribute to individual differences in schizophrenia symptom domains, bipolar disorder mood cycling, treatment‐resistant anxiety, and methylphenidate response variability in ADHD. Unlike pan‐dopaminergic agents, highly selective D3R modulation offers unprecedented therapeutic precision: antagonists ameliorate positive symptoms and cognitive deficits without extrapyramidal side effects, while partial agonists like cariprazine stabilize mood and mitigate anhedonia. These findings collectively underscore D3R as a transformative biomarker and druggable target for next‐generation precision therapeutics in psychiatry. 10.1002/ffj.70113 http://onlinelibrary.wiley.com/termsAndConditions#vor
title The Role of Dopamine Receptor 3 in Neuropsychiatric Disorders: A Brief Narrative Review
topic Flavour and Fragrance Journal
url https://onlinelibrary.wiley.com/doi/10.1002/ffj.70113