Behavioral effects of bidirectional modulators of brain monoamines reserpine and d-amphetamine in zebrafish

Abstract

Brain monoamines play a key role in the regulation of behavior. Reserpine depletes monoamines, and causes depression and hypoactivity in humans and rodents. In contrast, d-amphetamine increases brain monoamines’ levels, and evokes hyperactivity and anxiety. However, the effects of these agents on behavior and in relation to monoamine levels remain poorly understood, necessitating further experimental studies to understand their psychotropic action. Zebrafish (Danio rerio) are rapidly emerging as a promising model organism for drug screening and translational neuroscience research. Here, we have examined the acute and long-term effects of reserpine and d-amphetamine on zebrafish behavior in the novel tank test. Overall, d-amphetamine (5 and 10 mg/L) evokes anxiogenic-like effects in zebrafish acutely, but not 7 days later. In contrast, reserpine (20 and 40 mg/L) did not evoke overt acute behavioral effects, but markedly reduced activity 7 days later, resembling motor retardation observed in depression and/or Parkinson’s disease. Three-dimensional ‘temporal’ (X, Y, Time) reconstructions of zebrafish locomotion further supports these findings, confirming the utility of 3D-based video-tracking analyses in zebrafish models of drug action. Our results show that zebrafish are highly sensitive to drugs bi-directionally modulating brain monoamines, generally paralleling rodent and clinical findings. Collectively, this emphasizes the potential of zebrafish tests to model complex brain disorders associated with monoamine dysregulation.

The Integration of Sociality, Monoamines, and Stress Neuroendocrinology in Fish Models: Applications in the Neurosciences

“…It has been proposed that serotonergic projections to the telencephalon compute the aversive expectation value necessary for the zebrafish to mount an active response to aversive stimuli (Amo et al, 2014). Consistent with that hypothesis, drugs which increase 5-HT levels in the zebrafish brain increase anxiety-like behaviour in the light/dark test and decrease it in the novel tank test (Egan et al, 2009;Sackerman et al, 2010;Maximino et al, 2011Maximino et al, , 2013bMaximino et al, , 2014aIturriaga-Vásquez et al, 2012;Kyzar et al, 2013;Stewart et al, 2013;Herculano & Maximino, 2014;Cheng et al, 2016). Moreover, there is a correlation between 5-HT levels in the extracellular fluid ex vivo and behaviour in the light/dark test, with higher levels associated with more anxiety-like behaviour in the light/dark test and lower anxiety-like behaviour in the novel tank test (Maximino et al, 2013b).…”

“…Some roles for dopamine receptors have been described in zebrafish anxiety-like behaviour. Treatment with the dopamine transporter blocker D-amphetamine increases anxiety-like behaviour in the novel tank test without apparent locomotor effects (Kyzar et al, 2013). Similarly, the D 1 receptor antagonist SCH 23390 decreases anxiety-like behaviour (Kacprzak et al, 2017) and reduces social preference (Scerbina et al, 2012) in zebrafish.…”

Zebrafish: a novel model in neuropsychopharmacological research

“…The drug evokes strong pro-depressant effects in humans, besides causing hypo activity, motor stereotypies, lethargy, and anhedonia in rodent. 13 Reserpine treatment and related neurochemical and behavioural deficits are frequently used as a model of depression in rodents, but can likewise induce depressionlike behaviour in zebrafish (including hypolocomotion and disrupted shoaling, resembling motor retardation and social withdrawal symptoms observed in clinical depression).…”

SiO2nanoparticles cause depression and anxiety-like behavior in adult zebrafish

“…The rationale for the concentration of reserpine was based on previous research concerning the effective doses of reserpine on behavior of zebrash. 23 In this study, mild doses: 1 mg mL À1 (low concentration) and 10 mg mL À1 (high concentration) were chosen (Fig. 1c).…”

“…22 Currently, reserpine exposure is the widely accepted pharmacological manipulation method which is reported to induce depression-like phenotypes in zebrash. 23 Zebrash exposed to reserpine demonstrated longterm depressive symptoms, such as elevated baseline whole-body cortisol, social withdrawal and locomotion retardation.…”