Ketamine Upregulates the Glutamatergic Synaptic Pathway and Induces Zebrafish Addiction
10.13865/j.cnki.cjbmb.2024.06.1052
- VernacularTitle:氯胺酮上调谷氨酸能突触通路诱导斑马鱼成瘾
- Author:
Song QIAN
1
,
2
;
Si-Qi ZHU
;
Jin-Zhong XU
;
Cheng-Yu FANG
;
Yin-Ze CHAI
;
Yang LUO
;
Kai WANG
;
Yi-Zhou LIU
Author Information
1. 浙江警察学院刑事科学技术系,杭州 310053
2. 浙江省毒品防控技术研究重点实验室,杭州 310053
- Keywords:
ketamine;
zebrafish;
transcriptome;
glutaminergic synapse;
addiction
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(8):1153-1160
- CountryChina
- Language:Chinese
-
Abstract:
Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.
