Cocaine Differentially Affects Mitochondrial Function Depending on Exposure Time

Wattad, Sahar; Bryant, Gabriella; Shmuel, Miriam; Smith, Hannah L.; Yaka, Rami; Thornton, Claire

Abstract

Cocaine use is a rising global concern, and increased use is accompanied by
a significant increase in people entering treatment for the first time. However, there are
still no complete therapies, and preclinical tools are necessary to both understand the
action of cocaine and mitigate for its effects. Cocaine exposure rapidly impacts cellular
and mitochondrial health, leading to oxidative stress. This study evaluated the effects of
acute, repeated, and chronic cocaine exposure on C17.2 neural precursor cells. A single
exposure to high concentrations of cocaine caused rapid cell death, with lower concentrations
increasing markers of oxidative stress and mitochondrial dysfunction within 4 h of
exposure. Alterations in cellular bioenergetics and mitochondrial fusion and fission gene
expression (OPA1, DRP1) were also observed, which returned to baseline by 24 h after
insult. Repeated exposure over 3 days reduced cell proliferation and spare mitochondrial
respiratory capacity, suggesting compromised cellular resilience. Interestingly, chronic
exposure over 4 weeks led to cellular adaptation and restoring mitochondrial bioenergetics
and ATP production while mitigating for oxidative stress. These findings highlight the timedependent
cellular effects of cocaine, with initial toxicity and mitochondrial impairment
transitioning to adaptive responses under chronic exposure.

Citation

Wattad, S., Bryant, G., Shmuel, M., Smith, H. L., Yaka, R., & Thornton, C. (in press). Cocaine Differentially Affects Mitochondrial Function Depending on Exposure Time. International Journal of Molecular Sciences, 26(5), 2131. https://doi.org/10.3390/ijms26052131

• Journal Article Type: Article
• Acceptance Date: Feb 23, 2025
• Online Publication Date: Feb 27, 2025
• Deposit Date: Mar 6, 2025
• Publicly Available Date: Mar 13, 2025
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 5
• Pages: 2131
• DOI: https://doi.org/10.3390/ijms26052131