Using pharmacological interventions, flies have been used to assess the contribution of gamma-aminobutyric acid type B receptor subunits [GABA(B) receptors or GABBR] to response to alcohol. There are two GABA(B) receptor subunits in human, GABBR1 and GABBR2. There are three orthologous genes in Drosophila, GABA-B-R1, GABA-B-R2, and GABA-B-R3; see also the Gene Group report GABA(B) RECEPTORS (FBgg0000078). Multiple genetic reagents, including RNAi-targeting constructs and alleles caused by insertional mutagenesis, have been generated for the Drosophila genes.
Neither human gene, GABBR1 nor GABBR2, has been introduced into flies.
Using adult flies, sensitivity and tolerance to ethanol have been characterized after administration of GABBR agonists and antagonists, when compared with flies treated with ethanol alone. Dose-dependent increases and decreases in sensitivity to ethanol were observed for agonist and antagonist, respectively. The rate of tolerance development was increased by the agonist SKF-97451 and unaltered in presence of antagonist CGP-54626. Administration of the GABBR agonist 3-APMPA (independent of ethanol exposure) results in distinct behavioral phenotypes; partial knockdown of Dmel\GABA-B-R1, effected by RNAi via abdominal injection, suppresses these phenotypes.
[updated Mar. 2021 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
GABBR1 and GABBR2 encode subunits of the heterodimeric GABA(B) receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. [Gene Cards, GABBR1, GABBR2; 2021.03.21]
Both GABBR1 and GABBR2 exhibit highest levels of expression in the brain. [NCBI Gene, GABBR1, GABBR2; 2021.03.21]
One to one: 1 human gene to 1 Drosophila gene; additional related genes in both species.
One to one: 1 human gene to 1 Drosophila gene; additional related genes in both species.
High-scoring ortholog of human GABBR2 (1 Drosophila to 1 human); additional related genes in both species. Dmel\GABA-B-R1 shares 36% identity and 52% similarity with the human gene.
High-scoring ortholog of human GABBR1 (1 Drosophila to 1 human); additional related genes in both species. Dmel\GABA-B-R1 shares 49% identity and 69% similarity with the human gene.
