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Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

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Abstract

Rationale

The zebrafish dopaminergic system is thought to be evolutionarily conserved and may be amenable to pharmacological manipulation using drugs developed for mammalian receptors. However, only few studies have examined the role of specific receptor subtypes in behaviour of adult zebrafish.

Objectives

The objectives of this study are to determine the translational relevance of the zebrafish and examine the psychopharmacology of specific dopamine receptors in this species.

Methods

Using a behavioural pharmacological approach, we examine the effect of D1 and D2/3 receptor antagonisms on motor patterns of adult zebrafish during acute drug exposure and withdrawal.

Results

Acute exposure to SCH-23390 (D1 receptor antagonist) decreased total distance travelled in a dose-dependent manner. Exposure to amisulpride (D2/3 receptor antagonist) induced a biphasic dose-response in total distance travelled and in angular velocity. The results provide support for the existence of structurally and functionally conserved postsynaptic D1 and D2 receptors, as well as presynaptic D2 autoreceptors in the zebrafish brain. The behavioural effects of the employed antagonists did not persist following 30 min of withdrawal.

Conclusion

The results suggest that zebrafish, a cheaper and simpler model organism compared to the rat and the mouse, may be an efficient translationally relevant tool for the analysis of the psychopharmacology of receptors of the vertebrate dopaminergic system.

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Acknowledgments

This study is supported by an NSERC Discovery grant (#311637) issued to R.G.

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Authors and Affiliations

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

    Steven Tran & Robert Gerlai

  2. Department of Psychology, University of Toronto Mississauga, Mississauga, Canada

    Magda Nowicki, Arrujyan Muraleetharan & 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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  4. Robert Gerlai
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Correspondence to Steven Tran.

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Tran, S., Nowicki, M., Muraleetharan, A. et al. Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses. Psychopharmacology 232, 795–806 (2015). https://doi.org/10.1007/s00213-014-3713-0

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  • DOI: https://doi.org/10.1007/s00213-014-3713-0

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