Cocaethylene synthesis in Drosophila.
Cocaethylene is an active cocaine metabolite that targets mammalian neural reward pathways and thus contributes to the reinforcing and addictive properties of ethanol and cocaine. Using gas chromatography-mass spectrometry, we find that fruit flies (Drosophila melanogaster) possess a cellular mechanism through which cocaine can be converted to cocaethylene, presumably via ethanol-sensitive enzymes. These findings illustrate the striking similarity of gene products in humans and flies, which might reflect a homologous role in the metabolic inactivation of cocaine. Further, this conservation of metabolic steps suggests that Drosophila can be used to study cellular, molecular and biochemical processes leading to polydrug abuse and addiction.
Torres
G
G
Department of Psychology, State University of New York at Buffalo, 14260, USA. gtorres@acsu.buffalo.edu
Horowitz
J M
JM
D000818:Animals; D001711:Biotransformation; D003042:Cocaine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008956:Models, Chemical; D013045:Species Specificity
D018765:Dopamine Uptake Inhibitors; D000431:Ethanol; C066444:cocaethylene; D003042:Cocaine