Steven Tran1, Diptendu Chatterjee2, Amanda Facciol2, Robert Gerlai3,4. 1. Department of Cell & Systems Biology, University of Toronto, 3359 Mississauga Road North, DV 1022D, Mississauga, Ontario, L5L 1C6, Canada. stevenhuy.tran@mail.utoronto.ca. 2. Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, Ontario, L5L 1C6, Canada. 3. Department of Cell & Systems Biology, University of Toronto, 3359 Mississauga Road North, DV 1022D, Mississauga, Ontario, L5L 1C6, Canada. robert_gerlai@yahoo.com. 4. Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, Ontario, L5L 1C6, Canada. robert_gerlai@yahoo.com.
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.
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.
Authors: Josiane W Bortolotto; Giana P Cognato; Raissa R Christoff; Laura N Roesler; Carlos E Leite; Luiza W Kist; Mauricio R Bogo; Monica R Vianna; Carla D Bonan Journal: Zebrafish Date: 2014-02-25 Impact factor: 1.985
Authors: Tim Ruhl; Nicole Prinz; Nadine Oellers; Nathan Ian Seidel; Annika Jonas; Onder Albayram; Andras Bilkei-Gorzo; Gerhard von der Emde Journal: Psychopharmacology (Berl) Date: 2014-03-18 Impact factor: 4.530