Pseudoephedrine hydrochloride causes hyperactivity in zebrafish via modulation of the serotonin pathway

Yini Zhou; Tonglaga Li; Shangzi Zhou; Han Xu; Xiaoyu Yin; Hao Chen; Xuan Ni; Meirong Bai; Wuliji Ao; Jingfeng Yang; R G Ahmed; Xuefu Zhang; Shuyin Bao; Jianhua Yu; Kevin W H Kwok; Wu Dong

doi:10.1007/s11011-022-01042-0

Pseudoephedrine hydrochloride causes hyperactivity in zebrafish via modulation of the serotonin pathway

Metab Brain Dis. 2022 Oct;37(7):2559-2568. doi: 10.1007/s11011-022-01042-0. Epub 2022 Jul 30.

Authors

Yini Zhou^#¹, Tonglaga Li^#², Shangzi Zhou¹, Han Xu¹, Xiaoyu Yin¹, Hao Chen¹, Xuan Ni¹, Meirong Bai³, Wuliji Ao³, Jingfeng Yang¹, R G Ahmed⁴, Xuefu Zhang⁵, Shuyin Bao⁵, Jianhua Yu⁶, Kevin W H Kwok^{7

8}, Wu Dong⁹

Affiliations

¹ Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, 028000, Tongliao, Inner Mongolia, China.
² Affiliated Hospital of Inner Mongolia Minzu University, 028000, Tongliao, China.
³ College of Mongolian Medicine and Pharmacy, Inner Mongolia Minzu University, 028000, Tongliao, China.
⁴ Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
⁵ The Medical College of Inner Mongolia Minzu University, 028000, Tongliao, Inner Mongolia, China.
⁶ Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, 028000, Tongliao, Inner Mongolia, China. yjhyjh926@163.com.
⁷ Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong. kwh.kwok@polyu.edu.hk.
⁸ Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Hong Kong. kwh.kwok@polyu.edu.hk.
⁹ Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, 028000, Tongliao, Inner Mongolia, China. dongwu@imun.edu.com.

^# Contributed equally.

PMID: 35907131
DOI: 10.1007/s11011-022-01042-0

Abstract

This study aimed to explore behavioral changes of embryonic and larval zebrafish caused by pseudoephedrine hydrochloride (PSE) and its underlying mechanism. Zebrafish embryos were exposed to 0.5 µM, 2 µM, and 8 µM PSE at 4 h post-fertilization (4 hpf) or 22-23 hpf. Mortality, hatching rate, coiling frequency, heart rate, behavior changes, and related gene expression were observed at different developmental stages. PSE below 8 µM did not affect zebrafish mortality, hatching rate, and heart rate compared with the control group. For embryos, PSE caused an increase at 16-32 hpf in zebrafish coiling frequency which could be rescued by serotonin antagonist WAY100635. Similarly, PSE caused an increase in the swimming distance of zebrafish larvae at 120 hpf. PSE also elevated the expression of serotonin (5-HT)-related genes 5-htr1ab and tph2 and dopamine-related gene dbh. Behavioral changes in zebrafish embryos and larvae caused by PSE may be closely associated with increased expression of 5-HT and dopamine-related genes. This may be reflected that the behavioral changes in zebrafish are a possible PSE monitoring indicator.

Keywords: Behavioral changes; Dopamine; Pseudoephedrine hydrochloride; Serotonin; Zebrafish embryos.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dopamine / metabolism
Embryo, Nonmammalian* / metabolism
Larva / metabolism
Pseudoephedrine / metabolism
Serotonin / metabolism
Zebrafish* / genetics
Zebrafish* / metabolism

Substances

Serotonin
Pseudoephedrine
Dopamine