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Differential effects of acute administration of SCH-23390, a D1 receptor antagonist, and of ethanol on swimming activity, anxiety-related responses, and neurochemistry of zebrafish

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Abstract

Rationale

The zebrafish has become an increasingly popular animal model for investigating ethanol’s actions in the brain and its effects on behavior. Acute exposure to ethanol in zebrafish has been shown to induce a dose-dependent increase of locomotor activity, to reduce fear- and anxiety-related behavioral responses, and to increase the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC).

Objectives

The objective of the present study was to investigate the role of dopamine D1 receptors (D1-R) in ethanol-induced locomotor activity in zebrafish.

Methods

Zebrafish were pre-treated with SCH-23390 (0 or 1 mg/L bath concentration), a D1-R antagonist, and subsequently exposed to ethanol (0, 0.25, 0.5, 1.0 % v/v). To explore potential underlying mechanisms, we quantified levels of dopamine, DOPAC, serotonin, and 5-HIAA from whole-brain tissue using high-precision liquid chromatography.

Results

We found pre-treatment with the D1-R antagonist to attenuate locomotor activity independent of ethanol concentration. Furthermore, unlike ethanol, D1-R antagonism did not alter behavioral responses associated with fear and anxiety. Pre-treatment with SCH-23390 decreased levels of dopamine and DOPAC, but this effect was also independent of ethanol concentration. The D1-R antagonist also reduced serotonin and 5-hydroxyindole acetic acid (5-HIAA) levels.

Conclusion

These results suggest a multifaceted and at least partially independent role of dopamine D1 receptors in ethanol-induced locomotor activity and anxiety-related responses as well as in the functioning of the dopaminergic and serotoninergic neurotransmitter systems in zebrafish.

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Acknowledgments

This study was supported by an NSERC Discovery Grant (#311637) issued to RG and an NSERC CGSD issued to ST. We would like to thank Niveen Fulcher for her assistance with behavioral testing.

Ethical statement

The research reported here was reviewed and approved by the Local Animal Care Committee (LACC) of the University of Toronto Mississauga and is in accordance with the guidelines of the Canadian Council for Animal Care (CCAC).

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Authors and Affiliations

  1. Department of Cell and Systems Biology, University of Toronto Mississauga, 3359 Mississauga Road North, DV 1022D, Mississauga, ON, L5L 1C6, Canada

    Steven Tran & Robert Gerlai

  2. Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, ON, L5L 1C6, Canada

    Magda Nowicki, Arrujyan Muraleetharan, Diptendu Chatterjee & Robert Gerlai

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  1. Steven Tran
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  2. Magda Nowicki
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  3. Arrujyan Muraleetharan
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  5. Robert Gerlai
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Correspondence to Steven Tran or Robert Gerlai.

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Tran, S., Nowicki, M., Muraleetharan, A. et al. Differential effects of acute administration of SCH-23390, a D1 receptor antagonist, and of ethanol on swimming activity, anxiety-related responses, and neurochemistry of zebrafish. Psychopharmacology 232, 3709–3718 (2015). https://doi.org/10.1007/s00213-015-4030-y

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