Researchers at Brown U found that alcohol hijacks a conserved memory pathway in the brain and changes which versions of genes are made, forming the cravings that fuel addiction

Alcohol Activates Scabrous-Notch to Influence Associated Memories. Emily Petruccelli et al. Neuron, October 25, 2018. https://doi.org/10.1016/j.neuron.2018.10.005

Highlights
    •  Alcohol cue preference requires Scabrous-Notch interaction in mushroom body neurons
    •  Alcohol activates Notch and Su(H) target gene expression in the adult brain
    •  Dopamine 2 receptor splicing and targeting by Su(H) are altered by alcohol exposure
    •  Alcohol cue preference affects mushroom body gene expression and splicing

Summary: Drugs of abuse, like alcohol, modulate gene expression in reward circuits and consequently alter behavior. However, the in vivo cellular mechanisms through which alcohol induces lasting transcriptional changes are unclear. We show that Drosophila Notch/Su(H) signaling and the secreted fibrinogen-related protein Scabrous in mushroom body (MB) memory circuitry are important for the enduring preference of cues associated with alcohol’s rewarding properties. Alcohol exposure affects Notch responsivity in the adult MB and alters Su(H) targeting at the dopamine-2-like receptor ( Dop2R). Alcohol cue training also caused lasting changes to the MB nuclear transcriptome, including changes in the alternative splicing of Dop2R and newly implicated transcripts like Stat92E. Together, our data suggest that alcohol-induced activation of the highly conserved Notch pathway and accompanying transcriptional responses in memory circuitry contribute to addiction. Ultimately, this provides mechanistic insight into the etiology and pathophysiology of alcohol use disorder.

Press release: http://news.brown.edu/articles/2018/10/alcohol