title: Anxiolytic effects of diphenyl diselenide on adult zebrafish in a novelty paradigm.
abstract: Anxiety-related disorders are frequently observed in the population. Because the available pharmacotherapies for anxiety can cause side effects, new anxiolytic compounds have been screened using behavioral tasks. For example, diphenyl diselenide (PhSe)2, a simple organoselenium compound with neuroprotective effects, has demonstrated anxiolytic effects in rodents. However, this compound has not yet been tested in a novelty-based paradigm in non-mammalian animal models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on the behavior of adult zebrafish under novelty-induced stress. The animals were pretreated with 0.1, 0.25, 0.5, and 1μM (PhSe)2 in the aquarium water for 30min. The fish were then exposed to a novel tank, and their behavior was quantified during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration-dependent manner. At 0.01 and 0.25μM, (PhSe)2 did not elicit effects on fish behavior. At 0.5μM, moderate behavioral side effects (e.g., lethargy and short episodic immobility) were noted. At the highest concentration tested (1μM), dramatic side effects were observed, such as burst behavior and longer periods of immobility. The results were confirmed by spatiotemporal analysis of each group. Occupancy plot data showed dispersed homebase formation in the 0.25μM (PhSe)2-treated group compared with the control group (treated with 0.04% DMSO). Furthermore, animals treated with 0.25μM (PhSe)2 showed a reduction in latency to enter the top and spent more time in the upper area of the tank. These data suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of anxiety evoked by novelty.
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil; Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ibrahim
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil. Electronic address: ben_hurmussulini@yahoo.com.br.
authors.forename: Ben Hur M
authors.initials: BH
authors.lastname: Mussulini
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Moro
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: de Assis
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN), 90035-003 Porto Alegre, RS, Brazil; Programa de Pós Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS CEP 97105-900, Brazil.
authors.forename: Denis B
authors.initials: DB
authors.lastname: Rosemberg
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Diogo L
authors.initials: DL
authors.lastname: de Oliveira
authors.affiliation: Programa de Pós Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS CEP 97105-900, Brazil.
authors.forename: Joao B T
authors.initials: JB
authors.lastname: Rocha
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, 13565-905, São Carlos, SP, Brazil.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Schwab
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, P.O. Box 15003, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Schneider
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil; Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN), 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Eduardo P
authors.initials: EP
authors.lastname: Rico
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy*; D001555:Benzene Derivatives / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D016566:Organoselenium Compounds / Q000009:adverse effects / Q000494:pharmacology*; D011897:Random Allocation; D013315:Stress, Psychological / Q000188:drug therapy*; D015027:Zebrafish
chemical_list: D014151:Anti-Anxiety Agents; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; C061132:diphenyldiselenide
keywords: Anxiety; Diphenyl diselenide; Homebase; Spatiotemporal; Zebrafish