title: Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid.
abstract: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders primarily characterized by impaired social interaction and communication, and by restricted repetitive behaviors and interests. Ligands of histamine receptor 3 (H3R) are considered potential therapeutic agents for the treatment of different brain disorders and cognitive impairments. Considering this, the aim of the present study is to evaluate the actions of ciproxifan (CPX), an H3R antagonist, on the animal model of autism induced by prenatal exposure to valproic acid (VPA). Swiss mice were prenatally exposed to VPA on embryonic day 11 and assessed for social behavior, nociceptive threshold and repetitive behavior at 50 days of life. The treatment with CPX (3 mg/kg) or saline was administered 30 minutes before each behavioral test. The VPA group presented lower sociability index compared to VPA animals that were treated with CPX. Compared to the Control group, VPA animals presented a significantly higher nociceptive threshold, and treatment with CPX was not able to modify this parameter. In the marble burying test, the number of marbles buried by VPA animals was consistent with markedly repetitive behavior. VPA animals that received CPX buried a reduced amount of marbles. In summary, we report that an acute dose of CPX is able to attenuate sociability deficits and stereotypies present in the VPA model of autism. Our findings have the potential to help the investigations of both the molecular underpinnings of ASD and of possible treatments to ameliorate the ASD symptomatology, although more research is still necessary to corroborate and expand this initial data.
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Postgraduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Baronio
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Postgraduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Kamila
authors.initials: K
authors.lastname: Castro
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Taylor
authors.initials: T
authors.lastname: Gonchoroski
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Gabriela Mueller
authors.initials: GM
authors.lastname: de Melo
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Gustavo Della Flora
authors.initials: GD
authors.lastname: Nunes
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Victorio
authors.initials: V
authors.lastname: Bambini-Junior
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.affiliation: Translational Research Group in Autism Spectrum Disorders, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Postgraduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Research Group in Neuroglial Plasticity, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Child Neurology Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Rudimar
authors.initials: R
authors.lastname: Riesgo
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D018100:Receptors, Histamine H3 / Q000737:chemistry* / Q000378:metabolism; D014635:Valproic Acid / Q000633:toxicity
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3; C115705:ciproxifan; D014635:Valproic Acid