ArticleProceedings of the National Academy of Sciences of the United States of America2003
Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-beta gamma dimers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed, 83 citations in OpenAlex.
- Molecular mechanisms of alcohol's effects on the human body: A review and update.Journal of biochemical and molecular toxicology · 2023Review
- Endogenous μ-opioid-Neuropeptide Y Y1 receptor synergy silences chronic postoperative pain in mice.PNAS nexus · 2023Article
- Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.Frontiers in psychiatry · 2019Review
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Targeting G protein coupled receptor-related pathways as emerging molecular therapies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Review
- G-protein βγ subunit dimers modulate kidney repair after ischemia-reperfusion injury in rats.Molecular pharmacology · 2014Article
- Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: A possible role for plasticity in adenosine receptors.Behavioural brain research · 2014Article
- Article
- Molecular targeting of Gα and Gβγ subunits: a potential approach for cancer therapeutics.Trends in pharmacological sciences · 2013Review
- Signaling pathways mediating alcohol effects.Current topics in behavioral neurosciences · 2013Review
- Effects of A₂A adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats.Psychopharmacology · 2012Article
- Understanding molecular recognition by G protein βγ subunits on the path to pharmacological targeting.Molecular pharmacology · 2011Review
- Direct-reversible binding of small molecules to G protein βγ subunits.Biochimica et biophysica acta · 2011Article
- Implication of the purinergic system in alcohol use disorders.Alcoholism, clinical and experimental research · 2011Review
- Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers.Pharmacology, biochemistry, and behavior · 2011Article
- Adenosine A(2A) Receptors and A(2A) Receptor Heteromers as Key Players in Striatal Function.Frontiers in neuroanatomy · 2011Article
- Ionic storm in hypoxic/ischemic stress: can opioid receptors subside it?Progress in neurobiology · 2010Review
- Signal transduction via cannabinoid receptors.CNS & neurological disorders drug targets · 2009Review
- Adenosine A(2A) receptors in psychopharmacology: modulators of behavior, mood and cognition.Current neuropharmacology · 2009Article
- Tuning and fine-tuning of synapses with adenosine.Current neuropharmacology · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The mesolimbic dopamine system and cAMP-dependent/protein kinase A (PKA) pathways are strongly implicated in addictive behaviors. Here we determine the role of dopamine D2 receptors (D2) in PKA signaling responses to delta-opioid (DOR) and cannabinoid (CB1) receptors. We find in NG108-15/D2 cells and in cultured primary neurons that a brief exposure to saturating concentrations of DOR and CB1 agonists increases cAMP, promotes PKA C alpha translocation and increases cAMP-dependent gene expression. Activation of PKA signaling is mediated by Gi-beta gamma dimers. Importantly, subthreshold concentrations of DOR or CB1 agonists with D2 agonists, which are without effect when added separately, together activate cAMP/PKA signaling synergistically. There is also synergy between DOR or CB1 with ethanol, another addicting agent. In all instances, synergy requires adenosine activation of adenosine A2 receptors and is mediated by beta gamma dimers. Synergy by this molecular mechanism appears to confer hypersensitivity to opioids and cannabinoids while simultaneously increasing the sensitivity of D2 signaling when receptors are expressed on the same cells. This mechanism may account, in part, for drug-induced activation of medium spiny neurons in the nucleus accumbens.
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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.