In human and vertebrate model systems, extensive research supports a role for the neuropeptide NPY in modulating neurobiological responses to alcohol and to other drugs of abuse. NPY is known to interact with four G protein-coupled receptor subtypes: NPY1R, NPY2R, NPY4R, and NPY5R. The orthologous neuropeptide in Drosophila is NPF, which acts via Dmel\NPFR, a member of the Neuropeptide Y receptor family. RNAi-targeting constructs and alleles created by targeted recombination, including an amorphic allele, have been generated for Dmel\NPF. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\NPFR.
The human Hsap\NPY neuropeptide precursor gene has been introduced into flies in the context of a neuronal marker; it has not been used to characterize the role of NPY in response to alcohol. None of the related human neuropeptide receptors has been introduced into flies.
RNAi-effected reduction in either Dmel\NPF or Dmel\NPFR results in neurophysiology phenotypes (assayed in adult olfactory receptor neurons) and behavioral phenotypes; in the case of NPFR, memory defective phenotypes are reported. RNAi directed against NPFR results in decreased alcohol sensitivity; overexpression of NPF results in the opposite phenotype. In adults, conditional disruption of neurons that normally express NPF or NPFR rapidly confers resistance to ethanol sedation, suggesting that the NPF/NPFR neuronal pathway mediates the acute alcohol response. In experiments characterizing reward responses in flies, it was found that artificial activation of NPF neurons was in itself rewarding; this suggests that the NPF/NPFR system may function as a component of a general reward system.
[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]
Neuropeptide Y (NPY) encodes a neuropeptide that functions through G protein-coupled receptor(s); it is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. [Gene Cards, NPY; 2018.01.18]
NPY is currently known to interact with four G protein-coupled receptor subtypes: NPY1R, NPY2R, NPY4R, and NPY5R (Robinson and Thiele, 2017; pubmed:29056151).
No orthologs identified by standard algorithms; multiple neuropeptide precursor genes in both species. Literature supports orthology of human NPY and Dmel\NPF.
Many to many; multiple in both species.
Many to many; multiple in both species.
Many to many; multiple in both species.
Many to many; multiple in both species.
Low-scoring ortholog of multiple neuropeptide receptors in human; the NPY receptor genes, NPY1R, NPY2R, NPY4R and NPY5R, are among the more closely related. Dmel\NPFR shares 25-32% identity and 42-51% similarity with these human NPY receptor genes.
No orthologs identified by standard algorithms; literature supports orthology of human NPY and Dmel\NPF. Amino acid alignment against the human neuropeptide precusor for NPY shows 28% identity and 43% similarity; of similar size, align along ~60-65% of their length.
