ArticlePloS one2013
Cocaine inhibits dopamine D2 receptor signaling via sigma-1-D2 receptor heteromers.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 134 citations in OpenAlex.
- Article
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Exploring Tetrahydroisoquinoline (THIQ) Scaffold as Therapeutic Modulators of Sigma Receptors.Mini reviews in medicinal chemistry · 2025Review
- Amylovis-201 is a new dual-target ligand, acting as an anti-amyloidogenic compound and a potent agonist of theActa pharmaceutica Sinica. B · 2024Article
- Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.The European journal of neuroscience · 2024Article
- Discovery of AD258 as a Sigma Receptor Ligand with Potent Antiallodynic Activity.Journal of medicinal chemistry · 2023Article
- Sigma-1 receptor and seizures.Pharmacological research · 2023Review
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Age-dependent effects of social isolation on mesolimbic dopamine release.Experimental brain research · 2022Article
- Is Illicit Substance Use Gender-Specific? The Basic Points of Mental and Health Disorders.Toxics · 2022Review
- Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.Cellular and molecular neurobiology · 2022Review
- Recreational drug use and prospective memory.Psychopharmacology · 2022Article
- An Increase in Peripheral Temperature following Cocaine Administration Is Mediated through Activation of Dopamine D2 Receptor in Rats.Life (Basel, Switzerland) · 2022Article
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- Multi-Target Directed Ligands (MTDLs) Binding the σInternational journal of molecular sciences · 2021Review
- Evaluation of SubstitutedMolecules (Basel, Switzerland) · 2021Article
- Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole.International journal of molecular sciences · 2021Article
- Methamphetamine Blocks Adenosine AInternational journal of molecular sciences · 2021Article
- Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia.Molecules (Basel, Switzerland) · 2021Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain.
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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.