title: Concentration, population, and context-dependent effects of AM251 in zebrafish.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Cell & Systems Biology, University of Toronto, 3359 Mississauga Road North, DV 1022D, Mississauga, Ontario, L5L 1C6, Canada. stevenhuy.tran@mail.utoronto.ca.
authors.forename: Steven
authors.initials: S
authors.lastname: Tran
authors.affiliation: Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, Ontario, L5L 1C6, Canada.
authors.forename: Diptendu
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, Ontario, L5L 1C6, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Facciol
authors.affiliation: Department of Cell & Systems Biology, University of Toronto, 3359 Mississauga Road North, DV 1022D, Mississauga, Ontario, L5L 1C6, Canada. robert_gerlai@yahoo.com.|Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, CC4004, Mississauga, Ontario, L5L 1C6, Canada. robert_gerlai@yahoo.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Gerlai
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010880:Piperidines / Q000494:pharmacology* / Q000633:toxicity; D011720:Pyrazoles / Q000494:pharmacology* / Q000633:toxicity; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D015027:Zebrafish
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; C103505:AM 251; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine
keywords: AM251; Anxiety; CB1 receptor; Dopamine; Serotonin