ArticleAlcoholism, clinical and experimental research2018
Effects of Long-Term Alcohol Drinking on the Dopamine D2 Receptor: Gene Expression and Heteroreceptor Complexes in the Striatum in Rats.
Article in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Role of microRNAs in the pathophysiology of addiction.Wiley interdisciplinary reviews. RNA · 2021Pooled it
- Synergistic Effect of Combination Treatment of Brexpiprazole and Nalmefene on Ethanol Intake in Rats.Neuropsychopharmacology reports · 2026Article
- PACAP Signalling Network in the Nucleus Accumbens Core Regulates Reinstatement Behaviour in Rat.Addiction biology · 2025Article
- Monocyte-Derived Macrophages Expressing Dopamine D2-Subtype Receptors Drive Alcohol Effects on Mesolimbic Neurons and Microglia.Biomedicines · 2025Article
- A single-cell genomic atlas for the effects of chronic ethanol exposure in the mouse dorsal striatum.Molecular psychiatry · 2025Article
- Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors.Addiction neuroscience · 2024Article
- Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.INNOSC theranostics & pharmacological sciences · 2024Article
- Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.Gene & protein in disease · 2024Article
- The Roles of Endogenous D2R Dopamine and μ-opioid Receptors of the Brain in Alcohol use Disorder.Current medicinal chemistry · 2024Review
- Evidence for the existence of facilitatory interactions between the dopamine D2 receptor and the oxytocin receptor in the amygdala of the rat. Relevance for anxiolytic actions.Frontiers in pharmacology · 2023Article
- Neurogenetics and Epigenetics of Loneliness.Psychology research and behavior management · 2023Review
- Combined treatment with Sigma1R and A2AR agonists fails to inhibit cocaine self-administration despite causing strong antagonistic accumbal A2AR-D2R complex interactions: the potential role of astrocytes.Frontiers in molecular neuroscience · 2023Article
- The mGluMolecular neurobiology · 2022Article
- Dopaminylation in Psychostimulant Use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression.Current psychopharmacology · 2022Article
- Gut microbiota dysbiosis: The potential mechanisms by which alcohol disrupts gut and brain functions.Frontiers in microbiology · 2022Review
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- Exploring regulation and function of dopamine D3 receptors in alcohol use disorder. A PET [Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Adolescent oxycodone exposure inhibits withdrawal-induced expression of genes associated with the dopamine transmission.Addiction biology · 2021Article
- Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice.Nutrients · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent.
methodsA validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age-matched alcohol-naïve control rats. Reverse transcriptase quantitative PCR was used to quantify isoform-specific Drd2 gene expression levels. Using bisulfite pyrosequencing, DNA methylation levels of a regulatory region of the Drd2 gene were determined. In situ proximity ligation assay was used to measure densities of D2R receptor complexes: D2R-D2R, adenosine A2A receptor (A2AR)-D2R, and sigma1 receptor (sigma1R)-D2R.
resultsLong-term voluntary alcohol drinking significantly reduced mRNA levels of the long D2R isoform in the nucleus accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence of the Drd2 gene. Alcohol drinking also reduced the striatal density of D2R-D2R homoreceptor complexes, increased the density of A2AR-D2R heteroreceptor complexes in the NAc shell and the dorsal striatum, and decreased the density of sigma1R-D2R heteroreceptor complexes in the dorsal striatum.
conclusionsThe present results on long-term alcohol drinking might reflect reduced D2R levels through reductions in D2R-D2R homoreceptor complexes and gene expression. Furthermore, based on antagonistic interactions between A2AR and D2R, an increased density of A2AR-D2R heteroreceptor complexes might indicate a reduced affinity and signaling of the D2R population within the complex. Hence, both reduced striatal D2R levels and reduced D2R protomer affinity within the striatal A2AR-D2R complex might underlie reduced D2R radioligand binding in humans with AUD. This supports the hypothesis of a hypodopaminergic system in AUD and suggests the A2AR-D2R heteroreceptor complex as a potential novel treatment target.
Indexed as
Identifiers
What OpenQuestion holds
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.