Role of the serotonergic system in ethanol-induced aggression and anxiety: A pharmacological approach using the zebrafish model

Müller, Talise E.; Ziani, Paola Rampelotto; Fontana, Bárbara D.; Duarte, Tâmie; Stefanello, Flavia V.; Canzian, Julia; Santos, Adair R.S.

doi:10.1016/j.euroneuro.2019.12.120

Cited by 17 publications

(10 citation statements)

References 61 publications

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“…Apomorphine, a non-selective agonist of the D3 dopamine receptor, induced anxiolytic effects in zebrafish larvae (Ek et al, 2016). In the same way, partial agonists as aripiprazole and busperidone also decreased anxiety (Barcellos et al, 2020;Müller et al, 2020). Some of our results are in line with what was observed in these previous studies.…”

Section: Quantification Of Neurotransmitter Levelssupporting

confidence: 92%

Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish

Nabinger

Altenhofen

Buatois

et al. 2022

Preprint

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The dopaminergic neurotransmitter system is involved in numerous brain functions and behavioral processes. Alterations in this neurotransmitter system are associated with the pathogenesis of several human neurological disorders. Pharmacological agents that interact with the dopaminergic system allow the investigation of dopamine- mediated cellular and molecular responses and may elucidate the biological bases of such disorders. The zebrafish, a translationally relevant biomedical research organism, has been successfully employed in prior psychopharmacology studies. Here, we evaluate the effects of quinpirole (a dopamine D2/D3 receptor agonist) in adult zebrafish on behavioral parameters and neurotransmitter levels. Adult zebrafish received intraperitoneal injections of 0.5, 1.0, or 2.0 mg/kg of quinpirole or saline (control group) twice with an inter-injection interval of 48h. All tests were performed 24h after the second injection. After acute quinpirole administration, zebrafish exhibited decreased locomotor activity, increased anxiety-like behaviors and memory impairment compared to control. However, the quinpirole administration did not affect social and aggressive behavior. Quinpirole-treated fish exhibited altered swimming patterns: fish showed stereotypic swimming characterized by repetitive behavior, swimming from corner to corner at the bottom of the tank preceded and followed by episodes of immobility. Moreover, analysis of neurotransmitter levels in the brain demonstrated a significant increase in glutamate and a decrease in serotonin, while no alterations were observed in dopamine. These findings demonstrate that dopaminergic signaling altered by quinpirole administration results in significant changes in behavior and neurotransmitter levels in the central nervous system of zebrafish. Thus, we conclude that the use of quinpirole administration in adult zebrafish may be an appropriate tool for the analysis of mechanisms underlying neurological disorders related to the dopaminergic system.

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Section: Quantification Of Neurotransmitter Levelssupporting

confidence: 92%

Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish

Nabinger

Altenhofen

Buatois

et al. 2022

Preprint

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“…Some authors interpret this reaction (“bottom dwelling”) to novelty as anxiety-related behavior [ 34 , 39 , 40 , 41 ]. Treatment of zebrafish with pCPA (2 × 300 mg/kg pCPA, ip) increases anxiety in the novel tank diving test and decreased time spent in the tank’s upper third [ 37 , 42 ]. This result agrees with an increase of anxiety in Tph2KI mice with TPH2 deficiency [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

Evsiukova

Базовкина

Bazhenova

et al. 2021

IJMS

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The mechanisms of resistance to antidepressant drugs is a key and still unresolved problem of psychopharmacology. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play a key role in the therapeutic effect of many antidepressants. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT synthesis in the brain. We used zebrafish (Danio rerio) as a promising model organism in order to elucidate the effect of TPH2 deficiency caused by p-chlorophenylalanine (pCPA) on the alterations in behavior and expression of 5-HT-related (Tph2, Slc6a4b, Mao, Htr1aa, Htr2aa) and BDNF-related (Creb, Bdnf, Ntrk2a, Ngfra) genes in the brain after prolonged treatment with two antidepressants, inhibitors of 5-HT reuptake (fluoxetine) and oxidation (pargyline). In one experiment, zebrafish were treated for 72 h with 0.2 mg/L fluoxetine, 2 mg/L pCPA, or the drugs combination. In another experiment, zebrafish were treated for 72 h with 0.5 mg/L pargyline, 2 mg/L pCPA, or the drugs combination. Behavior was studied in the novel tank diving test, mRNA levels were assayed by qPCR, 5-HT and its metabolite concentrations were measured by HPLC. The effects of interaction between pCPA and the drugs on zebrafish behavior were observed: pCPA attenuated “surface dwelling” induced by the drugs. Fluoxetine decreased mRNA levels of Tph2 and Htr2aa genes, while pargyline decreased mRNA levels of Slc6a4b and Htr1aa genes. Pargyline reduced Creb, Bdnf and Ntrk2a genes mRNA concentration only in the zebrafish treated with pCPA. The results show that the disruption of the TPH2 function can cause a refractory to antidepressant treatment.

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“…Yet, during the early life stages of development, a partial agonist of the D2 dopamine receptor was found to induce anxiety-like behavior in zebrafish larvae (Félix et al, 2017a(Félix et al, , 2017b. However, the administration of partial agonists of D2 and D3 receptors in adult zebrafish has been shown to either have an anxiolytic and anxiogenic effect (Barcellos et al, 2020;De Campos et al, 2015;Ek et al, 2016;Johnson and Hamilton, 2017;Müller et al, 2020;Pittman and Hylton, 2015;Riehl et al, 2011). In addition to the effects related to anxiety, partial agonists of D2 receptors have also been found to reduce aggression and disrupt shoaling in zebrafish (Michelotti et al, 2018;Riehl et al, 2011;Zakhary et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Long-lasting behavioral effects of quinpirole exposure on zebrafish

Nabinger

Altenhofen

Peixoto

et al. 2021

Neurotoxicology and Teratology

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Role of the serotonergic system in ethanol-induced aggression and anxiety: A pharmacological approach using the zebrafish model

Cited by 17 publications

References 61 publications

Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish

Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

Long-lasting behavioral effects of quinpirole exposure on zebrafish

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