ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: σ1-D1-H3 receptor complexes as key targets for reducing cocaine's effects.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
- Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders.npj drug discovery · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Exploring Tetrahydroisoquinoline (THIQ) Scaffold as Therapeutic Modulators of Sigma Receptors.Mini reviews in medicinal chemistry · 2025Review
- ADHD and Risk of Precocious Puberty: Considering the Impact of MPH.Biomedicines · 2024Article
- Histamine HBiomolecules · 2024Review
- Discovery of AD258 as a Sigma Receptor Ligand with Potent Antiallodynic Activity.Journal of medicinal chemistry · 2023Article
- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
- The piperazine analogue para-fluorophenylpiperazine alters timing of the physiological effects of the synthetic cannabinoid receptor agonist AMB-FUBINACA, without changing its discriminative stimulus, signalling effects, or metabolism.Pharmacology, biochemistry, and behavior · 2023Article
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Effect of moderate prenatal ethanol exposure on the differential expression of two histamine H3 receptor isoforms in different brain regions of adult rat offspring.Frontiers in neuroscience · 2023Article
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- An open-like conformation of the sigma-1 receptor reveals its ligand entry pathway.Nature communications · 2022Article
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Multi-Target Directed Ligands (MTDLs) Binding the σInternational journal of molecular sciences · 2021Review
- Histamine HBiological psychiatry · 2021Article
- Region-specific regulation of central histaminergic H3 receptor expression in a mouse model of cow's milk allergy.Brain research · 2020Article
- Modulation of dopamine DeLife · 2020Article
- The histidine decarboxylase model of tic pathophysiology: a new focus on the histamine HBritish journal of pharmacology · 2020Review
- The Molecular Function of σ Receptors: Past, Present, and Future.Trends in pharmacological sciences · 2019Review
- Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine.
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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.