• alcohol use disorder

Several investigations studying mutations that affect ethanol sedation sensitivity in Drosophila support a role for the neuropeptide Corazonin (Dmel\Crz), and a small group of Corazonin-producing neurosecretory cells in the brain, in this response.

In the initial study (see FBhh0001119), loss-of-function mutations of the gene apt were found to exhibit decreased ethanol sedation sensitivity; neuronal expression of apt was found to be required for normal ethanol sedation sensitivity. To define specific neurons in which apt function is required to regulate this function, a collection of GAL4 lines expressed in the brain were used to express apt RNAi in small sets of neurons within the brain. Ethanol sedation sensitivity is dramatically reduced using the neuropeptidergic driver corazonin-GAL4 (Crz-GAL4), identifying 14 neurosecretory cells located in 2 bilateral groups within the pars lateralis of the fly brain.

Flies with reduced Crz expression, effected by RNAi, were then assessed; they show reduced sensitivity to ethanol sedation. Ablation of the Crz-expressing neurons also results in reduced sensitivity to ethanol sedation.

In a second study (see FBhh0001118), Atg16 mutant animals were found to more resistant to sedation upon exposure to ethanol than control flies. The Atg16 function in ethanol sensitivity also maps to the Corazonin-producing neurosecretory cells: normal ethanol sedation sensitivity could be restored in Atg16 mutants by targeted expression of wild-type Atg16 only in these neurosecretory cells. Atg16 deficiency impairs production of the Crz neuropeptide.

See also the human disease model report 'alcohol, response to, NPY-related' (FBhh0000704), which describes another neuropeptide involved in response to ethanol.

[updated Oct. 2019 by FlyBase; FBrf0222196]