ArticleBiological psychiatry2014
Selective overexpression of dopamine D3 receptors in the striatum disrupts motivation but not cognition.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Blonanserin versus haloperidol in Japanese patients with schizophrenia: A phase 3, 8-week, double-blind, multicenter, randomized controlled study.Neuropsychopharmacology reports · 2019Trial
- Vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors.Nature neuroscience · 2025Article
- Meta-Analysis of the Effect of Blonanserin in Treating Patients with Schizophrenia.Noro psikiyatri arsivi · 2025Review
- Spatial and Temporal Abnormalities of Spontaneous Fixational Saccades and Their Correlates With Positive and Cognitive Symptoms in Schizophrenia.Schizophrenia bulletin · 2024Article
- HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk.Viruses · 2022Article
- Potential Mechanisms for Why Not All Antipsychotics Are Able to Occupy Dopamine DFrontiers in psychiatry · 2022Review
- MicroRNAs as Critical Biomarkers of Major Depressive Disorder: A Comprehensive Perspective.Biomedicines · 2021Review
- Evidence of an interaction betweenEuropean psychiatry : the journal of the Association of European Psychiatrists · 2021Article
- Disruptions in effort-based decision-making following acute optogenetic stimulation of ventral tegmental area dopamine cells.Learning & memory (Cold Spring Harbor, N.Y.) · 2021Article
- Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders.Biomolecules · 2021Review
- Neuroinflammation and glial cell activation in mental disorders.Brain, behavior, & immunity - health · 2020Review
- Negative Symptoms of Schizophrenia and Dopaminergic Transmission: Translational Models and Perspectives Opened by iPSC Techniques.Frontiers in neuroscience · 2020Review
- Alterations in effort-related decision-making induced by stimulation of dopamine DPsychopharmacology · 2019Article
- Disentangling the diverse roles of dopamine D2 receptors in striatal function and behavior.Neurochemistry international · 2019Review
- Inflammation-induced motivational changes: Perspective gained by evaluating positive and negative valence systems.Current opinion in behavioral sciences · 2018Article
- Effects of neonatal excitotoxic lesions in ventral thalamus on social interaction in the rat.European archives of psychiatry and clinical neuroscience · 2018Article
- Neural substrates underlying effort, time, and risk-based decision making in motivated behavior.Neurobiology of learning and memory · 2016Review
- Catecholamines and cognition after traumatic brain injury.Brain : a journal of neurology · 2016Review
- Altering the course of schizophrenia: progress and perspectives.Nature reviews. Drug discovery · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEvidence indicating an increase in dopamine D2 receptor (D2R) density and occupancy in patients with schizophrenia comes from positron emission tomography studies using ligands that bind both D2Rs and dopamine D3 receptors (D3Rs), questioning the role of D3Rs in the pathophysiology of the disease. Dopamine D3 receptor positron emission tomography ligands have recently been developed and antagonists with preferential affinity for D3R versus D2R are undergoing clinical evaluation. To determine if an increase in D3Rs in the striatum could produce phenotypes relevant to schizophrenia, we generated a transgenic model of striatal D3R overexpression.
methodsA bi-transgenic system was used to generate mice with increased D3Rs selectively in the striatum. Mice with overexpression of D3R were subjected to an extensive battery of behavioral tests, including several relevant to schizophrenia. Ligand binding and quantitative reverse transcription polymerase chain reaction methods were used to quantify the effect of D3R overexpression on dopamine D1 receptors (D1Rs) in the striatum.
resultsMice with overexpression of D3R show no abnormalities in basic behavioral functions or cognitive tests but do display a deficit in incentive motivation. This was associated with a reduction in striatal D1R ligand binding, driven by a downregulation at the level of transcription. Both motivation and D1R expression were rescued by switching off the transgene in adulthood.
conclusionsOverexpression of D3Rs in the striatum of mice does not elicit cognitive deficits but disrupts motivation, suggesting that changes in D3Rs may be involved in the negative symptoms of schizophrenia. These data imply that it will be important to evaluate the effects of D3R antagonists on motivational symptoms, which are not improved by currently available antipsychotic medications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.