title: Time-dependent interacting effects of caffeine, diazepam, and ethanol on zebrafish behaviour.
abstract: Zebrafish have become a popular animal model for behavioural pharmacology due to their small size, rapid development, and amenability to high throughput behavioural drug screens. Furthermore, water-soluble compounds can be administered via immersion of the fish in the drug solution, which provides a non-invasive drug delivery method. Numerous studies have demonstrated stimulant effects of alcohol. Diazepam and caffeine, on the other hand have been found to have inhibitory effect on locomotor activity in zebrafish. However, the time-dependent changes induced by these psychoactive drugs are rarely reported, and potential drug interactions have not been examined in zebrafish, despite the translational relevance of this question. In the current study, we examine time- and dose-dependent changes in zebrafish following exposure to caffeine, diazepam, and ethanol quantifying four different behavioural parameters over a 30min recording session. We subsequently analyze potential drug-drug interactions by co-administering the three drugs in different combinations. Our time-course and dose-response analyses for each of the three drugs represent so far the most detailed studies available serving as a foundation for future psychopharmacology experiments with zebrafish. Furthermore, we report significant interactions between the three drugs corroborating findings obtained with rodent models as well as in humans, providing translational relevance for the zebrafish model.
authors.affiliation: University of Toronto, Department of Cell and Systems Biology, Canada. Electronic address: stevenhuy.tran@mail.utoronto.ca.
authors.forename: Steven
authors.initials: S
authors.lastname: Tran
authors.affiliation: University of Toronto Mississauga, Department of Psychology, Canada.
authors.forename: Niveen
authors.initials: N
authors.lastname: Fulcher
authors.affiliation: University of Toronto Mississauga, Department of Psychology, Canada.
authors.forename: Magda
authors.initials: M
authors.lastname: Nowicki
authors.affiliation: University of Toronto Mississauga, Department of Psychology, Canada.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Desai
authors.affiliation: University of Toronto Mississauga, Department of Psychology, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tsang
authors.affiliation: University of Toronto Mississauga, Department of Psychology, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Facciol
authors.affiliation: University of Western Ontario, Department of Physiology and Pharmacology, Canada.
authors.forename: Hayden
authors.initials: H
authors.lastname: Chow
authors.affiliation: University of Toronto, Department of Cell and Systems Biology, Canada; University of Toronto Mississauga, Department of Psychology, Canada. Electronic address: robert_gerlai@yahoo.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Gerlai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D013997:Time Factors; D015027:Zebrafish / Q000502:physiology*
chemical_list: D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D002110:Caffeine; D000431:Ethanol; D003975:Diazepam
keywords: Caffeine; Diazepam; Drug interaction; Ethanol; Time-dependent behavioural changes