TY - JOUR

T1 - Acute effects of amitriptyline on adult zebrafish

T2 - Potential relevance to antidepressant drug screening and modeling human toxidromes

AU - Demin, Konstantin A.

AU - Kolesnikova, Tatiana O.

AU - Khatsko, Sergey L.

AU - Meshalkina, Darya A.

AU - Efimova, Evgeniya V.

AU - Morzherin, Yuri Yu

AU - Kalueff, Allan V.

PY - 2017/7

Y1 - 2017/7

N2 - The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline. Overall, the drug at 1 and 5 mg/L significantly increased time spent in top and shortened the latency to enter it, thereby paralleling recent reports on zebrafish ‘serotonin toxicity-like behavior’ caused by various serotonergic agents. The 10 mg/L dose of the drug also significantly decreased top entries and maximal velocity and evoked overt ataxia, likely due to emerging non-specific toxic effects. Amitriptyline at 5 and 10 mg/L also dose-dependently increased serotonin turnover, but not noradrenaline levels, in zebrafish whole-brain samples. Overall, zebrafish high sensitivity to acute effects of amitriptyline can help improve our understanding of psychopharmacological profiles of this compound and the related CNS drugs, and contributes further to the development of aquatic experimental models of human toxidromes.

AB - The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline. Overall, the drug at 1 and 5 mg/L significantly increased time spent in top and shortened the latency to enter it, thereby paralleling recent reports on zebrafish ‘serotonin toxicity-like behavior’ caused by various serotonergic agents. The 10 mg/L dose of the drug also significantly decreased top entries and maximal velocity and evoked overt ataxia, likely due to emerging non-specific toxic effects. Amitriptyline at 5 and 10 mg/L also dose-dependently increased serotonin turnover, but not noradrenaline levels, in zebrafish whole-brain samples. Overall, zebrafish high sensitivity to acute effects of amitriptyline can help improve our understanding of psychopharmacological profiles of this compound and the related CNS drugs, and contributes further to the development of aquatic experimental models of human toxidromes.

KW - Amitriptyline

KW - Aquatic screening

KW - Serotonin syndrome

KW - Serotonin toxicity

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85019084876&partnerID=8YFLogxK

U2 - 10.1016/j.ntt.2017.04.002

DO - 10.1016/j.ntt.2017.04.002

M3 - Article

C2 - 28438663

VL - 62

SP - 27

EP - 33

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

ER -