TY - JOUR

T1 - Chronic digoxin exposure causes hyperactivity, anxiolysis, and alters brain monoamine content in zebrafish (Danio rerio)

AU - Kazanskaya, Rogneda B.

AU - Ilyin, Nikita P.

AU - Abaimov, Denis A.

AU - Derzhavina, Ksenia A.

AU - Demin, Konstantin A.

AU - Kalueff, Allan V.

AU - Gainetdinov, Raul R.

AU - Lopachev, Alexander V.

PY - 2025/1/8

Y1 - 2025/1/8

N2 - To investigate the effects of chronic exposure to the cardiotonic steroid digoxin on locomotor activity, anxiety, and brain tissue monoamine content in Zebrafish. In total 24 adult (3-5 months) wild-type experimentally naïve zebrafish (50 : 50 ratio of females to males) were housed in 4-L tanks, in groups of six animals per tank. Two μM Digoxin was maintained in half of the tanks for 7 days. The 'Novel tank test' was performed on day 7 and the animals were euthanized. Concentrations of dopamine, serotonin, and their metabolites were then quantified in brain tissue using HPLC-ED. Seven-day exposure to 2 μM water solution of digoxin caused robust hyperlocomotion and reduced anxiety-like behavior in adult zebrafish in the 'Novel tank test'. The treatment also evoked pronounced neurochemical responses in zebrafish, including increased whole-brain 3-methoxytyramine, reduced norepinephrine and serotonin, and unaltered dopamine, homovanillic acid or 5-hydroxyindoleacetic acid levels. Deficits in monoaminergic (dopaminergic, serotonergic, and noradrenergic) neurotransmission are a key pathogenetic factor for multiple neuropsychiatric and neurodegenerative diseases. Commonly used clinically to treat cardiac conditions, cardiotonic steroids can affect dopaminergic neurotransmission. Chronic exposure to digoxin evokes hyperactivity-like behavior accompanied by altered monoamine neurotransmission in zebrafish, which may be relevant to understanding the central nervous system side effects of cardiotonic steroids.

AB - To investigate the effects of chronic exposure to the cardiotonic steroid digoxin on locomotor activity, anxiety, and brain tissue monoamine content in Zebrafish. In total 24 adult (3-5 months) wild-type experimentally naïve zebrafish (50 : 50 ratio of females to males) were housed in 4-L tanks, in groups of six animals per tank. Two μM Digoxin was maintained in half of the tanks for 7 days. The 'Novel tank test' was performed on day 7 and the animals were euthanized. Concentrations of dopamine, serotonin, and their metabolites were then quantified in brain tissue using HPLC-ED. Seven-day exposure to 2 μM water solution of digoxin caused robust hyperlocomotion and reduced anxiety-like behavior in adult zebrafish in the 'Novel tank test'. The treatment also evoked pronounced neurochemical responses in zebrafish, including increased whole-brain 3-methoxytyramine, reduced norepinephrine and serotonin, and unaltered dopamine, homovanillic acid or 5-hydroxyindoleacetic acid levels. Deficits in monoaminergic (dopaminergic, serotonergic, and noradrenergic) neurotransmission are a key pathogenetic factor for multiple neuropsychiatric and neurodegenerative diseases. Commonly used clinically to treat cardiac conditions, cardiotonic steroids can affect dopaminergic neurotransmission. Chronic exposure to digoxin evokes hyperactivity-like behavior accompanied by altered monoamine neurotransmission in zebrafish, which may be relevant to understanding the central nervous system side effects of cardiotonic steroids.

UR - https://www.mendeley.com/catalogue/559f9e02-96ae-3c5e-8939-6a32bac3c4f0/

U2 - 10.1097/wnr.0000000000002120

DO - 10.1097/wnr.0000000000002120

M3 - Article

VL - 36

SP - 55

EP - 60

JO - NeuroReport

JF - NeuroReport

SN - 0959-4965

IS - 1

ER -