TY - JOUR

T1 - Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model

AU - Demin, Konstantin A

AU - Kolesnikova, Tatiana O

AU - Galstyan, David S

AU - Krotova, Nataliya A

AU - Ilyin, Nikita P

AU - Derzhavina, Ksenia A

AU - Levchenko, Nataliia A

AU - Strekalova, Tatyana

AU - de Abreu, Murilo S

AU - Petersen, Elena V

AU - Seredinskaya, Maria

AU - Cherneyko, Yulia V

AU - Kositsyn, Yuriy M

AU - Sorokin, Dmitry V

AU - Zabegalov, Konstantin N

AU - Mor, Mikael S

AU - Efimova, Evgeniya V

AU - Kalueff, Allan V

N1 - Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism.

AB - Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism.

KW - Animals

KW - Antidepressive Agents/pharmacology

KW - Behavior, Animal

KW - Disease Models, Animal

KW - Eicosapentaenoic Acid/metabolism

KW - Emotions

KW - Endotoxins/metabolism

KW - Fluoxetine/pharmacology

KW - Lipopolysaccharides/chemistry

KW - Neurochemistry/methods

KW - Norepinephrine/blood

KW - Phenotype

KW - Stress, Physiological

KW - Stress, Psychological/drug therapy

KW - Zebrafish

KW - CHRONIC MILD STRESS

KW - NEUROTRANSMITTER SYSTEMS

KW - DOCOSAHEXAENOIC ACID

KW - DOPAMINE

KW - PITUITARY-ADRENAL AXIS

KW - ANXIETY

KW - PROINFLAMMATORY CYTOKINES

KW - DEPRESSION-LIKE BEHAVIOR

KW - DOUBLE-BLIND

KW - NEUROSCIENCE RESEARCH

UR - http://www.scopus.com/inward/record.url?scp=85110430597&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/6d47bb6c-d9a2-38b4-8935-f5003d64a021/

U2 - 10.1038/s41598-021-92422-6

DO - 10.1038/s41598-021-92422-6

M3 - Article

C2 - 34253753

VL - 11

SP - 14289

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14289

ER -