Ephedrine and cocaine cause developmental neurotoxicity and abnormal behavior in zebrafish

Dong-Dong Ma; Wen-Jun Shi; Si-Ying Li; Jin-Ge Zhang; Zhi-Jie Lu; Xiao-Bing Long; Xin Liu; Chu-Shu Huang; Guang-Guo Ying

doi:10.1016/j.aquatox.2023.106765

Ephedrine and cocaine cause developmental neurotoxicity and abnormal behavior in zebrafish

Aquat Toxicol. 2023 Dec:265:106765. doi: 10.1016/j.aquatox.2023.106765. Epub 2023 Nov 11.

Authors

Dong-Dong Ma¹, Wen-Jun Shi², Si-Ying Li¹, Jin-Ge Zhang¹, Zhi-Jie Lu¹, Xiao-Bing Long¹, Xin Liu³, Chu-Shu Huang³, Guang-Guo Ying⁴

Affiliations

¹ SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China.
² SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China; Anti-Drug Technology Center of Guangdong Province and National Anti-Drug Laboratory Guangdong Regional Center, Guangdong Provincial Key Laboratory of Psychoactive Substances Monitoring and Safety, Guangzhou 510230, China. Electronic address: wenjun.shi@m.scnu.edu.cn.
³ Anti-Drug Technology Center of Guangdong Province and National Anti-Drug Laboratory Guangdong Regional Center, Guangdong Provincial Key Laboratory of Psychoactive Substances Monitoring and Safety, Guangzhou 510230, China.
⁴ SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China; Anti-Drug Technology Center of Guangdong Province and National Anti-Drug Laboratory Guangdong Regional Center, Guangdong Provincial Key Laboratory of Psychoactive Substances Monitoring and Safety, Guangzhou 510230, China. Electronic address: guangguo.ying@m.scnu.edu.cn.

PMID: 37979497
DOI: 10.1016/j.aquatox.2023.106765

Abstract

Ephedrine (EPH) and cocaine (COC) are illegal stimulant drugs, and have been frequently detected in aquatic environments. EPH and COC have negative effects on the nervous system and cause abnormal behaviors in mammals and fish at high concentrations, but their mechanisms of neurotoxicity remain unclear in larvae fish at low concentrations. To address this issue, zebrafish embryos were exposed to EPH and COC for 14 days post-fertilization (dpf) at 10, 100, and 1000 ng L^-1. The bioaccumulation, development, behavior, cell neurotransmitter levels and apoptosis were detected to investigate the developmental neurotoxicity (DNT) of EPH and COC. The results showed that EPH decreased heart rate, while COC increased heart rate. EPH caused cell apoptosis in the brain by AO staining. In addition, behavior analysis indicated that EPH and COC affected spontaneous movement, touch-response, swimming activity and anxiety-like behaviors. EPH and COC altered the levels of the neurotransmitters dopamine (DA) and γ-aminobutyric acid (GABA) with changes of the transcription of genes related to the DA and GABA pathways. These findings indicated that EPH and COC had noticeable DNT in the early stage of zebrafish at environmentally relevant concentrations.

Keywords: Abnormal behavior; Cocaine; Developmental neurotoxicity; Ephedrine.

MeSH terms

Animals
Cocaine* / metabolism
Cocaine* / toxicity
Ephedrine / metabolism
Ephedrine / toxicity
Larva
Mammals / metabolism
Neurotransmitter Agents / metabolism
Water Pollutants, Chemical* / toxicity
Zebrafish / metabolism
gamma-Aminobutyric Acid / metabolism

Substances

Ephedrine
Water Pollutants, Chemical
Cocaine
Neurotransmitter Agents
gamma-Aminobutyric Acid