title: Anxiolytic properties of N-acetylcysteine in mice.
abstract: Anxiety disorders are highly prevalent and often result in poor quality of life. Available anxiolytics show significant adverse effects as well as partial efficacy in a sizable part of patients. Innovative treatments with more favorable risk-benefit ratio are sorely needed. A growing body of clinical data indicates the benefits of N-acetylcysteine (NAC) in psychiatric conditions. NAC modulates antioxidant, glutamatergic, inflammatory and neurotrophic pathways in the central nervous system, all of which are relevant to anxiety pathology. We evaluated the effects of NAC in mice models commonly used to characterize anxiolytic compounds. Male adult CF1 or BALB/c mice were treated (i.p.) acutely or subacutely (4 consecutive days) with NAC (60-150mg/kg) 60min before open field, light/dark, hole-board, social interaction, elevated T-maze or stress-induced hyperthermia tests. Diazepam (2mg/kg) was used as positive control. We found that NAC presents anxiolytic effects in all models, except for the elevated T-maze. Subacute treatments resulted in lower effective doses in comparison to acute treatment. The anxiolytic effects of NAC were comparable to diazepam. NAC is a safe and low cost medicine with suggested benefits in psychiatric conditions often presenting co-morbidity with anxiety. This study contributes evidence to support the validity of clinical trials with NAC in the context of anxiety disorders, especially considering the safety profile in comparison to the limitations of diazepam for long term treatment.
authors.affiliation: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Santos
authors.affiliation: Grupo de Estudos Biológicos e Clínicos em Patologias Humanas, Universidade Federal da Fronteira Sul, Chapecó, SC, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Herrmann
authors.affiliation: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Radharani
authors.initials: R
authors.lastname: Benvenutti
authors.affiliation: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Noetzold
authors.affiliation: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Giongo
authors.affiliation: Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Clarissa S
authors.initials: CS
authors.lastname: Gama
authors.affiliation: Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Piato
authors.affiliation: Laboratório de Etnofarmacologia, Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: elaine.elisabetsky@gmail.com.
authors.forename: Elaine
authors.initials: E
authors.lastname: Elisabetsky
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy*; D001831:Body Temperature / Q000187:drug effects; D003623:Dark Adaptation / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005334:Fever / Q000209:etiology; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D003975:Diazepam; D000111:Acetylcysteine
keywords: Hole-board; Light/dark; N-acetylcysteine (NAC); Open field; Social interaction; Stress-induced hyperthermia