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Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models.
Sharghi, Shirin; Flunkert, Stefanie; Daurer, Magdalena; Rabl, Roland; Chagnaud, Boris Philippe; Leopoldo, Marcello; Lacivita, Enza; Hutter-Paier, Birgit; Prokesch, Manuela.
Afiliação
  • Sharghi S; Department of Neuropharmacology, QPS Austria GmbH, Grambach, Austria.
  • Flunkert S; Institute for Biology, Karl-Franzens-Universität Graz, Graz, Austria.
  • Daurer M; Department of Neuropharmacology, QPS Austria GmbH, Grambach, Austria.
  • Rabl R; Department of Neuropharmacology, QPS Austria GmbH, Grambach, Austria.
  • Chagnaud BP; Department of Neuropharmacology, QPS Austria GmbH, Grambach, Austria.
  • Leopoldo M; Institute for Biology, Karl-Franzens-Universität Graz, Graz, Austria.
  • Lacivita E; Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Bari, Italy.
  • Hutter-Paier B; Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Bari, Italy.
  • Prokesch M; Department of Neuropharmacology, QPS Austria GmbH, Grambach, Austria.
Front Neurosci ; 17: 1087788, 2023.
Article em En | MEDLINE | ID: mdl-37065917
Introduction: Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by two core behavioral symptoms: impaired social communication and interaction, as well as stereotypic, repetitive behavior. No distinct cause of ASD is known so far; however, excitatory/inhibitory imbalance and a disturbed serotoninergic transmission have been identified as prominent candidates responsible for ASD etiology. Methods: The GABA B receptor agonist R-Baclofen and the selective agonist for the 5HT7 serotonin receptor LP-211 have been reported to correct social deficits and repetitive behaviors in mouse models of ASD. To evaluate the efficacy of these compounds in more details, we treated BTBR T+ Itpr3 tf /J and B6.129P2-Fmr1 tm1Cgr /J mice acutely with R-Baclofen or LP-211 and evaluated the behavior of animals in a series of tests. Results: BTBR mice showed motor deficits, elevated anxiety, and highly repetitive behavior of self-grooming. Fmr1-KO mice exhibited decreased anxiety and hyperactivity. Additionally, Fmr1-KO mice's ultrasonic vocalizations were impaired suggesting a reduced social interest and communication of this strain. Acute LP-211 administration did not affect the behavioral abnormalities observed in BTBR mice but improved repetitive behavior in Fmr1-KO mice and showed a trend to change anxiety of this strain. Acute R-Baclofen treatment improved repetitive behavior only in Fmr1-KO mice. Conclusion: Our results add value to the current available data on these mouse models and the respective compounds. Yet, additional studies are needed to further test R-Baclofen and LP-211 as potential treatments for ASD therapy.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article