In a study of voluntary intake of various psychoactive substances using Drosophila, it was determined that long-term escalation of ethanol preference requires the dopamine receptor Dop1R1, specifically expression of Dop1R1 in the mushroom body of the brain. Dmel\Dop1R1 is orthologous to two dopamine receptor genes in human, DRD5 and DRD1. Amorphic mutations, RNAi-targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Dop1R1.
Neither human gene, DRD5 nor DRD1, has been introduced into flies.
Using a voluntary intake assay in Drosophila, animals carrying mutations in different dopamine receptor genes were tested. Loss-of-function mutation in Dop1R1, but not of the other receptors, results in failure to acquire experience-dependent ethanol preference. RNAi-mediated knockdown of Dop1R1 specifically in the mushroom body results in a a similar phenotype. Overexpression of Dop1R1 enhances ethanol preference in the voluntary intake assay. A small number of genetic and physical interactions have been described for Dop1R1; see below and in the Dop1R1 gene report.
See also the human disease model report 'alcohol, response to, dual-GPCR signaling' (FBhh0000904).
[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]
DRD1 and DRD5 receptors (also known as D1-like receptors) are a subset of the dopamine receptor G-protein-coupled receptor family that also includes DRD2, DRD3 and DRD4. DRD5 and DRD1 subtypes are G-protein coupled receptors which stimulate adenylyl cyclase. The DRD1 subtype is the most abundant dopamine receptor in the central nervous system. DRD5 is expressed in neurons in the limbic regions of the brain; DRD5 has a 10-fold higher affinity for dopamine than the DRD1 subtype [Gene Cards, DRD5, DRD1; 2021.03.09]
Many to one: 2 human genes to 1 Drosophila gene.
Many to one: 2 human genes to 1 Drosophila gene.
Moderate-scoring ortholog of human DRD5 and DRD1 (1 Drosophila to 2 human). Dmel\Dop1R1 shares 32-35% identity and 48-50% similarity with the human genes.
