The role of Microfibrillar Associated Protein 2 (MFAP2) and Notch1 in alcohol cravings
Despite alcohol being one of the most used and abused drugs worldwide, little is known of its direct molecular actions. Alcohol changes the expression of many genes in the brain, but the mechanisms underlying these transcriptional changes remain unknown. Further, it is unclear how ethanol affects cellular transcription during the development of appetitive memory for alcohol intoxication, potentially leading to cravings. We used an unbiased genetic approach in the fruit fly, Drosophila melanogaster, to reveal a role for fibrinogen-like Scabrous and cell membrane receptor Notch in regulating behaviors related to these cravings. We propose to test whether polymorphisms in the human homologs to these genes, MFAP2 or NOTCH1, are associated with differential reactivity to alcohol-associated cues in a fashion that may confer an increased susceptibility to alcohol use disorders (AUDs).