Long-term exposure to ephedrine leads to neurotoxicity and neurobehavioral disorders accompanied by up-regulation of CRF in prefrontal cortex and hippocampus in rhesus macaques

• Published in: Behavioural brain research Vol. 393; p. 112796
• Main Authors: Duan, Shouxing, Xie, Lei, Zheng, Lian, Huang, JinZhuang, Guo, RuiWei, Sun, ZongBo, Xie, Yao, Lv, JunYao, Lin, ZhiRong, Ma, Shuhua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2020
• Subjects: Behaviors; Corticotropin-releasing factor (CRF); Ephedrine; Neurotoxicity; Rhesus; Behaviors; Neurotoxicity; Corticotropin-releasing factor (CRF); Rhesus; Ephedrine
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2020.112796

•The chronic ephedrine toxicity model in rhesus macaques was established.•Ephedrine has neurotoxicity and can cause some specific neurobehavioral disorders.•CRF in the prefrontal cortex and hippocampus were increased in the ephedrine model.•The increased of CRF is associated with neurotoxicity of ephedrine Chun-hui Chang. Drug addiction continues to threaten the health and welfare of people worldwide, and ephedrine abuse is a serious drug problem in many areas of the world. Ephedrine toxicity is thought to induce behavioral effects primarily through actions on the central nervous system. The corticotropin-releasing factor (CRF) system plays an important role in regulating behavioral effects induced by addictive drugs, but whether CRF is related to ephedrine toxicity remains unclear. This study seeks to examine whether there is a correlation between the CRF and chronic ephedrine neurotoxicity. To this end, we established a chronic ephedrine (0.4–1.6 mg/kg/d) exposure model in rhesus macaques, assessed its effects on body weight and behavior, examined neuronal changes in the prefrontal cortex and hippocampus, and measured the CRF expression in the prefrontal cortex and hippocampus. After 8-weeks of exposure to ephedrine, the toxic effects of ephedrine included significant weight loss and induction of behavioral changes in rhesus macaques. In particular, in the modeling group, the abnormal behavioral changes mainly manifested as irritability and behavioral sensitization. Meanwhile, the histological abnormalities included neuronal morphological changes, pyknosis and irregular shapes of neurons in the prefrontal cortex and hippocampus. In addition, the expression levels of CRF mRNA and protein were increased in the prefrontal cortex and hippocampus of ephedrine-treated animals. In summary, the finding of this study indicated that ephedrine neurotoxicity can cause neuronal damage in cerebral cortex, which in turn can result in certain neurobehavioral abnormalities, and that CRF expression in prefrontal cortex and hippocampus is elevated in response to ephedrine exposure. These observations suggested that long-term exposure to ephedrine might be causing neurotoxicity and leading to neurobehavioral disorders accompanied by up-regulation of CRF in prefrontal cortex and hippocampus.