Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish

Neurotoxicology and Teratology
Bonnie L RobinsonJyotshna Kanungo

Abstract

Ketamine, a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1-0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reverse...Continue Reading

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Citations

Jul 18, 2019·Critical Reviews in Toxicology·Luís FélixLuís Antunes
Oct 11, 2019·Journal of Applied Toxicology : JAT·Bonnie L RobinsonJyotshna Kanungo
Jul 22, 2020·Journal of Applied Toxicology : JAT·Qiang GuJyotshna Kanungo
Jul 9, 2020·Nutrients·Alina KepkaNapoleon Waszkiewicz
Jan 26, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Linghua XieZhiyong Hu
Feb 12, 2021·Chemical Research in Toxicology·Leah E LathamFang Liu
Jul 22, 2018·Neuroscience Letters·Hector Rosas-HernandezSumit Sarkar
May 19, 2021·Journal of Applied Toxicology : JAT·Qiang Gu, Jyotshna Kanungo

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