Human gamma-aminobutyric acid A receptor alpha2 gene moderates the acute effects of alcohol and brain mRNA expression.
- Authors
- Haughey, H M; Ray, L A; Finan, P; Villanueva, R; Niculescu, M; Hutchison, K E
- Year
- 2008
- Journal
- Genes, brain, and behavior
- PMID
- 18005236
- DOI
- 10.1111/j.1601-183X.2007.00369.x
Gamma-aminobutyric acid A (GABA(A)) receptors moderate several of the behavioral effects of alcohol. In fact, recent studies have shown an association between the gene for the alpha2-subunit of the GABA(A) receptor (GABRA2) and alcoholism. In the present study, we examined the functional relevance of the GABRA2 gene in alcohol dependence by assessing brain GABRA2 mRNA and GABA(A)alpha2-subunit protein levels in post-mortem prefrontal cortical tissue collected from control and alcohol-dependent individuals. In addition, using an endophenotype approach, we tested whether the GABRA2 gene moderates sensitivity to the acute effects of alcohol in two independent samples from distinct human alcohol challenge studies. Results indicated that GABRA2 mRNA levels significantly differed by GABRA2 genotype. GABRA2 single nucleotide polymorphisms (rs573400, rs279871 and rs279858) were significantly associated with sensitivity to the acute effects of alcohol. Specifically, there was a significant main effect of GABRA2 x breath alcohol concentration on several measures of subjective responses to alcohol, including the hedonic value of alcohol. Importantly, reanalysis of a previous intravenous alcohol administration study confirmed the results of the oral alcohol challenge study. In summary, these results extend previous findings and provide new insights into the putative biobehavioral mechanisms that may moderate the association between the GABRA2 gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Effect of Ethanol on Brain Electrical Tissue Conductivity in Social Drinkers. | Cao J et al. | β | 2025 | β |
| Prospective DNA Methylation Analysis of the CpG GABRA2 Receptor Subunit in Alcohol Dependence during Detoxification. | Preuss UW et al. | β | 2022 | β |
| Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder. | Fish KN et al. | β | 2022 | β |
| Evidence for incentive salience sensitization as a pathway to alcohol use disorder. | CofresΓ RU et al. | β | 2019 | β |
| GABA<sub>A</sub> receptor polymorphisms in alcohol use disorder in the GWAS era. | Koulentaki M et al. | β | 2018 | β |
| GABRA2, alcohol, and illicit drug use: An event-level model of genetic risk for polysubstance use. | Mallard TT et al. | β | 2018 | β |
| Sex and Ξ²-Endorphin Influence the Effects of Ethanol on Limbic <i>Gabra2</i> Expression in a Mouse Binge Drinking Model. | Rhinehart EM et al. | β | 2018 | β |
| GABA<sub>A</sub> receptor subtype involvement in addictive behaviour. | Stephens DN et al. | β | 2017 | β |
| A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction. | Bell RL et al. | β | 2016 | β |
| Alcohol-Induced Stimulation Mediates the Effect of a GABRA2 SNP on Alcohol Self-Administrated among Alcohol-Dependent Individuals. | Boyd SJ et al. | β | 2016 | β |
| Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage. | HernΓ‘ndez JA et al. | β | 2016 | β |
| Mechanisms in the relation between GABRA2 and adolescent externalizing problems. | Wang FL et al. | β | 2016 | β |
| Potentiation of Gamma Aminobutyric Acid Receptors (GABAAR) by Ethanol: How Are Inhibitory Receptors Affected? | FΓΆrstera B et al. | β | 2016 | β |
| Association of GABAA receptor Ξ±2 subunit gene (GABRA2) with alcohol dependence-related aggressive behavior. | Strac DS et al. | β | 2015 | β |
| Association study of GABAA Ξ±2 receptor subunit gene variants in antipsychotic-associated weight gain. | Zai CC et al. | β | 2015 | β |
| Common single nucleotide variants underlying drug addiction: more than a decade of research. | BΓΌhler KM et al. | β | 2015 | β |
| Gene expression profile analysis of rat cerebellum under acute alcohol intoxication. | Zhang Y et al. | β | 2015 | β |
| Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases. | Yuan H et al. | β | 2015 | β |
| Motivational Effects of Methylphenidate are Associated with GABRA2 Variants Conferring Addiction Risk. | Duka T et al. | β | 2015 | β |
| Risky Business: Pathways to Progress in Biologically Informed Studies of Psychopathology. | Agrawal A et al. | β | 2015 | β |
| A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration. | Arias AJ et al. | β | 2014 | β |
| Dutasteride reduces alcohol's sedative effects in men in a human laboratory setting and reduces drinking in the natural environment. | Covault J et al. | β | 2014 | β |
| Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics. | Jin Z et al. | β | 2014 | β |
| Neuropathology of alcoholism. | Sutherland GT et al. | β | 2014 | β |
| Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug pictures. | BΓΌhler KM et al. | β | 2014 | β |
| The Genetics, Neurogenetics and Pharmacogenetics of Addiction. | Demers CH et al. | β | 2014 | β |
| Fyn-dependent gene networks in acute ethanol sensitivity. | Farris SP et al. | β | 2013 | β |
| Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication. | Blednov YA et al. | β | 2013 | β |
| Voluntary intravenous self-administration of alcohol detects an interaction between GABAergic manipulation and GABRG1 polymorphism genotype: a pilot study. | Plawecki MH et al. | β | 2013 | β |
| Alcohol Dependence and Genes Encoding Ξ±2 and Ξ³1 GABAA Receptor Subunits: Insights from Humans and Mice. | Borghese CM et al. | β | 2012 | β |
| Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration. | Dixon CI et al. | β | 2012 | β |
| Genetics of GABAergic signaling in nicotine and alcohol dependence. | Cui WY et al. | β | 2012 | β |
| Identifying genetic variation for alcohol dependence. | Agrawal A et al. | β | 2012 | β |
| Introduction to the special issue "Pharmacotherapies for the treatment of alcohol abuse and dependence" and a summary of patents targeting other neurotransmitter systems. | Bell RL et al. | β | 2012 | β |
| Pharmacogenetically driven treatments for alcoholism: are we there yet? | Arias AJ et al. | β | 2012 | β |
| Ξ±2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders. | Engin E et al. | β | 2012 | β |
| Genetic association study of GABRA2 single nucleotide polymorphisms and electroencephalography in alcohol dependence. | Lydall GJ et al. | β | 2011 | β |
| Genetics of alcohol dependence. | Kimura M et al. | β | 2011 | β |
| Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive Ξ±2-containing GABA(A) receptors. | Blednov YA et al. | β | 2011 | β |
| Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence. | Cosgrove KP et al. | β | 2011 | β |
| High risk groups often have higher levels of alcohol response than low risk: the other side of the coin. | Newlin DB et al. | β | 2010 | β |
| Pharmacogenetics of alcohol and alcohol dependence treatment. | Kranzler HR et al. | β | 2010 | β |
| Catching the alcohol buzz: an examination of the latent factor structure of subjective intoxication. | Ray LA et al. | β | 2009 | β |
| Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity. | Wang LL et al. | β | 2009 | β |
| The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress. | Kumar S et al. | β | 2009 | β |
| Toxicogenomics and clinical toxicology: an example of the connection between basic and applied sciences. | Ferrer-Dufol A et al. | β | 2009 | β |
| Assessment of GABAA benzodiazepine receptor (GBzR) sensitivity in patients with alcohol dependence. | Taylor C et al. | β | 2008 | β |
| The role of GABA(A) receptors in the development of alcoholism. | Enoch MA | β | 2008 | β |
| The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample. | Lind PA et al. | β | 2008 | β |