RT Conference Proceedings T1 Cocaine detrimentally affects mitochondrial functionality and cell viability in dopaminergic neurons. A1 Zamorano-González, Pablo A1 Bandini, Luca A1 Valverde, Nadia A1 Claros-Gil, Silvia A1 Romero-Zerbo, Silvana Yanina A1 Lara, Estrella A1 Santín-Núñez, Luis Javier A1 Martín-Montañez, Elisa A1 Gago-Calderón, Belén A1 García-Fernández, María Inmaculada K1 Cocaína - Efectos fisiológicos K1 Sistema dopaminérgico AB An elevated consumption of cocaine (benzoylmethylecgonine), which causes anesthetic andstimulant effects on the central nervous system, may be associated with severalneurodegenerative conditions affecting dopaminergic neurons, such as Parkinson's disease (PD).To investigate the impact of cocaine on cell viability and morphology, dopaminergic neurons fromthe substantia nigra (SN4741) were cultured. Analysis involved assessing cell death (LDH levels)and cell morphology (GIEMSA staining) after a 24-hour treatment period. Additionally, theeffects on reactive oxygen species (ROS) generation (DH2), membrane potential (JC-1), oxygenconsumption rate (OCR), and mitochondrial stress (Seahorse) were evaluated after a 6-hourtreatment. The optimal concentration of cocaine for experimental use (2 mM) was identified,inducing a substantial 39.75% neuronal death. Examination of neuronal death (LDH) revealed aremarkable 280% increase following cocaine treatment. Optical analysis demonstratedheightened mortality and detrimental changes in neuronal morphology post-cocaine treatment,including a globose shape, loss of synapses, extremely thin membrane, and cell aggregation. Inthe "short time" experiments, mitochondrial oxidative damage was evident in SN cells treatedwith cocaine, leading to the demise of 75% of the cells. Furthermore, a significant 173.6%increase in reactive oxygen species (ROS) production and a 20% reduction in mitochondrialmembrane potential (JC-1 assay) were observed. Cocaine treatment also resulted in a notable60% decrease in mitochondrial oxygen consumption. In summary, a concentration of 2 mMcocaine induces a considerable rise in mitochondrial oxidative damage, subsequently causingmorphological alterations and progressive death of dopaminergic neurons due to theaccumulation of reactive oxygen species (ROS). YR 2024 FD 2024 LK https://hdl.handle.net/10630/31991 UL https://hdl.handle.net/10630/31991 LA eng NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. DS RIUMA. Repositorio Institucional de la Universidad de Málaga RD 5 mar 2026