ArticleMolecular psychiatry2015
Evidence against dopamine D1/D2 receptor heteromers.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders.npj drug discovery · 2026Review
- Dopamine D1Aa and D2a Receptor Expression in the Auditory System of a Vocal Fish.The Journal of comparative neurology · 2026Article
- Dopamine D1Aa and D2a Receptor Expression in the Auditory System of a Vocal Fish.bioRxiv : the preprint server for biology · 2025Article
- The Role of Dopamine in Neurological, Psychiatric, and Metabolic Disorders and Cancer: A Complex Web of Interactions.Biomedicines · 2025Article
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- G Protein-Coupled Receptor Dimerization-What Next?International journal of molecular sciences · 2024Review
- Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis.Nature communications · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models.Frontiers in psychiatry · 2024Review
- Age-related changes of dopamine D1 and D2 receptors expression in parvalbumin-positive cells of the orbitofrontal and prelimbic cortices of mice.Frontiers in neuroscience · 2024Article
- Adenosine AFrontiers in pharmacology · 2024Article
- Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain.bioRxiv : the preprint server for biology · 2023Article
- Thrombospondin1 mimics rapidly relieve depression via Shank3 dependent uncoupling between dopamine D1 and D2 receptors.iScience · 2023Article
- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Roles of Pancreatic Islet Catecholamine Neurotransmitters in Glycemic Control and in Antipsychotic Drug-Induced Dysglycemia.Diabetes · 2023Review
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats.International journal of molecular sciences · 2022Article
- Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine's rewarding effects but preserves natural reward processing.Science advances · 2021Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation, because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer, ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout (KO) mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq KO mice, as well as in knock-in mice expressing a mutant Ala(286)-CaMKIIα that cannot autophosphorylate to become active. Moreover, we found that, in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1/D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies.
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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.