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]