This report describes characterization of the fly response to alcohol using Drosophila genes within the P13K/AKT signaling pathway. Neural perturbations of expression of fly genes Pi3K92E (orthologous to human PIK3C kinase catalytic subunit genes), Pdk1 (ortholog of human PDPK1 kinase), Akt (orthologous to human AKT kinase genes), and Pten (ortholog of human PTEN phosphatase) all produce changes in ethanol sensitivity.
In a genetic screen for mutants exhibiting altered sensitivity to the sedating effect of ethanol, an insertion allele of the fly gene aru exhibited hypersensitivity (see FBhh0000688). Since the human orthologs of aru, EPS8 and related genes, have been implicated in signaling via the PI3K/AKT pathway, additional Drosophila genes within these pathways were assessed for ethanol sensitivity in adult flies. Using a pan-neuronal driver, various overexpression, dominant gain-of-function, and RNAi-effected loss-of-function perturbations were tested.
[updated Jan. 2018 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]
Moderate- to high-scoring ortholog of human genes AKT2, AKT3, and AKT1 (1 Drosophila to 3 human). Dmel\Akt shares 60-64% identity and 75-77% similarity with these human genes.