Citation

Müller TE, Ziani PR, Fontana BD, Duarte T, Stefanello FV, Canzian J, Santos ARS, Rosemberg DB. Eur. Neuropsychopharmacol. 2020; ePub(ePub): ePub.

Affiliation

Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA. Electronic address: dbrosemberg@gmail.com.

Copyright

(Copyright © 2020, Elsevier Publishing)

DOI

10.1016/j.euroneuro.2019.12.120

PMID

31948829

Abstract

Acute ethanol (EtOH) consumption exerts a biphasic effect on behavior and increases serotonin levels in the brain. However, the molecular mechanisms underlying alcohol-mediated behavioral responses still remain to be fully elucidated. Here, we investigate pharmacologically the involvement of the serotonergic pathway on acute EtOH-induced behavioral changes in zebrafish. We exposed zebrafish to 0.25, 0.5, 1.0% (v/v) EtOH for 1 h and analyzed the effects on aggression, anxiety-like behaviors, and locomotion. EtOH concentrations that changed behavioral responses were selected to the subsequent experiments. As a pharmacological approach, we used pCPA (inhibitor of tryptophan hydroxylase), WAY100135 (5-HT_1A antagonist), buspirone (5-HT_1A agonist), CGS12066A and CGS12066B (5-HT_1B antagonist and agonist, respectively), ketanserin (5-HT_2A antagonist) and (±)-DOI hydrochloride (5-HT_2A agonist). All serotonergic receptors tested modulated aggression, with a key role of 5-HT_2A in aggressive behavior following 0.25% EtOH exposure. Because CGS12066B mimicked 0.5% EtOH anxiolysis, which was antagonized by CGS12066A, we hypothesized that anxiolytic-like responses are possibly mediated by 5-HT_1B receptors. Conversely, the depressant effects of EtOH are probably not related with direct changes on serotonergic pathway. Overall, our novel findings demonstrate a role of the serotonergic system in modulating the behavioral effects of EtOH in zebrafish. These data also reinforce the growing utility of zebrafish models in alcohol research and help elucidate the neurobiological mechanisms underlying alcohol abuse and associated complex behavioral phenotypes.

Copyright © 2020 Elsevier B.V. and ECNP. All rights reserved.

Language: en

Keywords

5-HT receptors; Alcohol abuse; Neurobehavioral phenotypes; Pharmacological intervention; Serotonin; Zebrafish