PUBLICATION
Acute exposure to N-Ethylpentylone induces developmental toxicity and dopaminergic receptor-regulated aberrances in zebrafish larvae
- Authors
- Fan, E., Xu, Z., Yan, J., Wang, F., Sun, S., Zhang, Y., Zheng, S., Wang, X., Rao, Y.
- ID
- ZDB-PUB-210306-8
- Date
- 2021
- Source
- Toxicology and applied pharmacology 417: 115477 (Journal)
- Registered Authors
- Wang, Xu
- Keywords
- Behavior, Developmental toxicity, Dopaminergic receptor, Heart rate, N-Ethylpentylone (NEP), Zebrafish larvae
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Benzodioxoles/toxicity*
- Butylamines/toxicity*
- Cardiovascular System/drug effects*
- Cardiovascular System/embryology
- Cardiovascular System/metabolism
- Dopamine/metabolism*
- Dopamine Agonists/toxicity*
- Female
- Gene Expression Regulation, Developmental
- Heart Rate/drug effects
- Larva/drug effects
- Larva/metabolism
- Locomotion/drug effects
- Male
- Nervous System/drug effects*
- Nervous System/embryology
- Nervous System/metabolism
- Receptors, Dopamine D1/agonists*
- Receptors, Dopamine D1/metabolism
- Receptors, Dopamine D2/agonists*
- Receptors, Dopamine D2/metabolism
- Transcription, Genetic
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/agonists*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 33667508 Full text @ Tox. App. Pharmacol.
- CTD
- 33667508
Citation
Fan, E., Xu, Z., Yan, J., Wang, F., Sun, S., Zhang, Y., Zheng, S., Wang, X., Rao, Y. (2021) Acute exposure to N-Ethylpentylone induces developmental toxicity and dopaminergic receptor-regulated aberrances in zebrafish larvae. Toxicology and applied pharmacology. 417:115477.
Abstract
N-Ethylpentylone (NEP) is one of the most recent novel stimulants, and there is limited understanding of its toxicity. Here we employed zebrafish model for analyzing the effects of NEP on early embryos and cardiovascular and nervous systems at late developmental stages. We first observed multi-malformations in early embryos and larvae after NEP administration, together with significant deregulations of brain and heart development-associated genes (neurog1, her6, elavl3, nkx2.5, nppa, nppb, tnnt2a) at transcriptional level. Low-dosed NEP treatment induced an anxiety-like phenotype in zebrafish larvae, while higher doses of NEP exerted an inhibitory effect on locomotion and heart rate. Besides, the expression of th (tyrosine hydroxylase) and th2 (tyrosine hydroxylase 2), identifying dopamine (DA) release, were significantly increased during one-hour free swimming after effective low-dosed NEP administration, along with the upregulation of gene fosab and fosb related to stress and anxiety response. D1R antagonist SCH23390 and D2R antagonist sulpiride partially alleviated the aberrances of locomotion and heart rate, indicating dopaminergic receptors were involved in the bidirectional dosage-dependent pattern of NEP-induced performance. Meanwhile, sulpiride offset the upregulated expression of th, th2 and fosab in the group of 1.5 μM NEP, which highlighted the significant role of D2R in NEP-induced locomotive effects. This study systematically described the developmental, neuronal and cardiac toxicity of NEP in zebrafish, and identified the dopaminergic receptors as one of the downstream effectors of NEP administration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping