Crack cocaine exposure leads to developmental alterations and mitochondrial dysfunction in the Drosophila...

Crack cocaine is a highly addictive drug that may induce a plethora of health problems in users.The underlying pathophysiological and toxicity mechanisms promoted by crack cocaine use are still unclear.Here, we used the Drosophila melanogaster model to evaluate the dose-dependent effects of crack cocaine ingestion on several developmental and lifelong parameters, as well as the expression levels of key mitochondrial, endoplasmic reticulum, and antioxidant genes.Canton-S flies were fed increasing concentrations of crack cocaine and subjected to development, longevity, and negative geotaxis assays.Subsequently, we analyzed gene expression in L3 larvae and adult heads by quantitative real-time PCR. Crack cocaine increased larval lethality (>80%), and it affected the locomotor abilities of both larvae and adults (20-30%).This was associated with increased levels of mtDNA and transcripts for Marf, Pink1, Catalase, and Sod2 at low concentrations, suggesting mitochondrial biogenesis and remodelling.Mitochondrial and ER stress were evident at high crack concentrations, as indicated by a decrease in mtDNA copy number and increased transcript levels of parkin, spargel, Ire1, PEK, and CaMKII.Taken together, our data suggest that crack cocaine may lead to distinct harmful effects that are often apparent at very low doses, increasing adverse outcomes at high doses.