title: Inhibition of phosphorylated tyrosine hydroxylase attenuates ethanol-induced hyperactivity in adult zebrafish (Danio rerio).
abstract: Zebrafish have been successfully employed in the study of the behavioural and biological effects of ethanol. Like in mammals, low to moderate doses of ethanol induce motor hyperactivity in zebrafish, an effect that has been attributed to the activation of the dopaminergic system. Acute ethanol exposure increases dopamine (DA) in the zebrafish brain, and it has been suggested that tyrosine hydroxylase, the rate-limiting enzyme of DA synthesis, may be activated in response to ethanol via phosphorylation. The current study employed tetrahydropapaveroline (THP), a selective inhibitor of phosphorylated tyrosine hydroxylase, for the first time, in zebrafish. We treated zebrafish with a THP dose that did not alter baseline motor responses to examine whether it can attenuate or abolish the effects of acute exposure to alcohol (ethanol) on motor activity, on levels of DA, and on levels of dopamine's metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). We found that 60-minute exposure to 1% alcohol induced motor hyperactivity and an increase in brain DA. Both of these effects were attenuated by pre-treatment with THP. However, no differences in DOPAC levels were found among the treatment groups. These findings suggest that tyrosine hydroxylase is activated via phosphorylation to increase DA synthesis during alcohol exposure in zebrafish, and this partially mediates alcohol's locomotor stimulant effects. Future studies will investigate other potential candidates in the molecular pathway to further decipher the neurobiological mechanism that underlies the stimulatory properties of this popular psychoactive drug.
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada.
authors.forename: Magda
authors.initials: M
authors.lastname: Nowicki
authors.affiliation: Department of Cell and System Biology, University of Toronto, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Tran
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada.
authors.forename: Diptendu
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Canada; Department of Cell and System Biology, University of Toronto, Canada. Electronic address: robert_gerlai@yahoo.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Gerlai
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006948:Hyperkinesis / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D013765:Tetrahydropapaveroline / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D015027:Zebrafish
chemical_list: D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol; D013765:Tetrahydropapaveroline; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Alcohol; Dopamine; Ethanol; Locomotor activity; Tyrosine hydroxylase; Zebrafish