ArticleMolecular psychiatry2011
Functional genetic variants that increase synaptic serotonin and 5-HT3 receptor sensitivity predict alcohol and drug dependence.
Article in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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
53 citing papers in PubMed, 102 citations in OpenAlex.
- A randomized, double-blind, placebo-controlled, pharmacogenetic study of ondansetron for treating alcohol use disorder.Alcoholism, clinical and experimental research · 2022Trial
- Determination of genotype combinations that can predict the outcome of the treatment of alcohol dependence using the 5-HT(3) antagonist ondansetron.The American journal of psychiatry · 2013Trial
- Trial
- Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial.CNS drugs · 2012Trial
- Decoding the serotonin-alcohol crosstalk: the role of central serotonergic dysregulation in alcohol use disorder.Pharmacological reports : PR · 2026Review
- Mental disorders in the Black population: a scoping review.Frontiers in public health · 2026Article
- Effect of serotonin receptor gene variants on substance use disorders.Annals of medicine · 2025Article
- Molecular Effect of Variants in Serotonin Transporter Gene in Women with Alcohol Use Disorder.Cells · 2025Article
- The role of brain serotonin signaling in excessive alcohol consumption and withdrawal: A call for more research in females.Neurobiology of stress · 2024Article
- Multi-animal-model study reveals mutations in neural plasticity and nociception genes linked to excessive alcohol drinking.Alcohol, clinical & experimental research · 2023Article
- Molecular Toxicology and Pathophysiology of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder Associated with Traumatic Brain Injury.International journal of molecular sciences · 2023Review
- Gut microbiota in alcohol-related liver disease: pathophysiology and gut-brain cross talk.Frontiers in pharmacology · 2023Review
- Alcohol Use Disorder: Neurobiology and Therapeutics.Biomedicines · 2022Review
- Serotonin ReceptorInternational journal of environmental research and public health · 2022Article
- Tapping into 5-HTInternational journal of molecular sciences · 2021Review
- Genetic Knockout of the Serotonin Reuptake Transporter Results in the Reduction of Dendritic Spines in In vitro Rat Cortical Neuronal Culture.Journal of molecular neuroscience : MN · 2021Article
- Serotonin system genes contribute to the susceptibility to obesity in Black adolescents.Obesity science & practice · 2021Article
- African American Children's Diminished Returns of Subjective Family Socioeconomic Status on Fun Seeking.Children (Basel, Switzerland) · 2020Article
- Reward Responsiveness in the Adolescent Brain Cognitive Development (ABCD) Study: African Americans' Diminished Returns of Parental Education.Brain sciences · 2020Article
- Ultrahigh-resolution MRI reveals structural brain differences in serotonin transporter knockout rats after sucrose and cocaine self-administration.Addiction biology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
The 5-HT3 receptor is rapidly potentiated by ethanol and mediates fast excitatory serotonin (5-HT) transmission that modulates dopamine release in the reward circuitry. The 5-HT transporter regulates synaptic 5-HT availability. Functional polymorphisms in genes encoding the transporter and receptor may therefore influence addiction vulnerability. In this study, 360 treatment-seeking African American male patients with single and comorbid DSM-IV lifetime diagnoses of alcohol, cocaine and heroin dependence and 187 African American male controls were genotyped for the triallelic 5-HTTLPR functional polymorphism in the 5-HT transporter gene (SLC6A4) and 16 haplotype-tagging single-nucleotide polymorphisms (SNPs) across HTR3B (including the functional rs1176744 Tyr129Ser) and HTR3A, genes encoding 5-HT3 receptors. The HTR3B rs1176744 gain-of-function Ser129 allele predicted alcohol dependence (P=0.002) and low 5-HTTLPR activity predicted cocaine/heroin dependence (P=0.01). Both the HTR3B Ser129 allele (P=0.014, odds ratio (OR)=1.7 (1.1-2.6)) and low 5-HTTLPR activity (P=0.011, OR=2.5 (1.3-4.6)) were more common in men with alcohol+drug dependence compared with controls. Moreover, the HTR3B Ser129 allele and low 5-HTTLPR activity had an additive (but not an interactive) effect on alcohol+drug dependence (OR=6.0 (2.1-16.6)) that accounted for 13% of the variance. One possible explanation of our findings is that increased synaptic 5-HT coupled with increased 5-HT3 receptor responsiveness may result in enhanced dopamine transmission in the reward pathway, a predictor of increased risk for addiction. Our results may have pharmacogenetic implications for 5-HT3 therapeutic antagonists such as ondansetron.
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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.