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Concentration, population, and context-dependent effects of AM251 in zebrafish

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Abstract

Rationale

The function of the cannabinoid type 1 receptor (CB1-R) is poorly understood in zebrafish, and numerous inconsistent effects have been reported on it in the literature.

Objective

The objective of the present study is to determine whether differences in the reported effects of CB1-R antagonism on anxiety-like behavioural responses, dopaminergic and serotonergic responses are due to concentration, context-dependent and/or population (genotype-related) effects.

Method

Two genetically distinct populations of zebrafish (AB and short fin (SF)) were treated with different concentrations of AM251 (0, 0.1, 1mg/L), and behavioural responses were quantified under two different contexts: one, following habituation and two, subsequently in a novel environment. The levels of dopamine, serotonin and their metabolites 3,4-dihydroxyindole acetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were quantified from whole-brain tissue.

Results

We demonstrate that a 60-min exposure to AM251 (0, 0.1, 1mg/L) does not alter behavioural performance following habituation in either populations. However, when subsequently transferred to a novel environment, zebrafish that were pre-treated with the highest dose of AM251 (1mg/L) exhibited increased anxiety-like behavioural responses including elevated absolute turn angle, freezing and bottom dwelling. We found that exposure to the highest dose of AM251 (1mg/L) for 60min increased serotonin in fish of both populations tested. In contrast, exposure to 0.1mg/L AM251 decreased, whereas to 1mg/L AM251 increased dopamine, DOPAC and 5-HIAA in fish of both populations.

Conclusion

Our results demonstrate a genotype-independent effect of AM251 but imply that the inconsistent findings obtained after pharmacological blockade of CB1-Rs in zebrafish may be due to a combination of concentration- and environmental context-dependent effects.

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Acknowledgments

The research was supported by an NSERC Discovery Grant (#311637) and a Brain Canada Foundation Grant issued to Robert Gerlai and an NSERC Canadian Graduate Scholarship (doctoral level) issued to Steven Tran.

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Authors and Affiliations

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

    Steven Tran & Robert Gerlai

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

    Diptendu Chatterjee, Amanda Facciol & Robert Gerlai

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  1. Steven Tran
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  2. Diptendu Chatterjee
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  3. Amanda Facciol
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  4. Robert Gerlai
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Correspondence to Steven Tran or Robert Gerlai.

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

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Tran, S., Chatterjee, D., Facciol, A. et al. Concentration, population, and context-dependent effects of AM251 in zebrafish. Psychopharmacology 233, 1445–1454 (2016). https://doi.org/10.1007/s00213-016-4240-y

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  • DOI: https://doi.org/10.1007/s00213-016-4240-y

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