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

Crack cocaine is a highly addictive drug that has psychomimetic properties and 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 Drosophila melanogaster as an experimental 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, L3 larvae and adult heads were processed for gene expression analysis 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, at low concentrations, increased levels of mtDNA and transcripts for Marf, Pink1, Catalase, and Sod2, suggesting mitochondrial biogenesis and remodeling, possibly due to mild oxidative stress. 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. Our research helps shed light on the complex underlying mechanisms of crack cocaine toxicity and might have health-related implications, contributing to possible future interventions for users.