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Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models

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/inhibitor...

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Autores principales: Sharghi, Shirin, Flunkert, Stefanie, Daurer, Magdalena, Rabl, Roland, Chagnaud, Boris Philippe, Leopoldo, Marcello, Lacivita, Enza, Hutter-Paier, Birgit, Prokesch, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097904/
https://www.ncbi.nlm.nih.gov/pubmed/37065917
http://dx.doi.org/10.3389/fnins.2023.1087788
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author Sharghi, Shirin
Flunkert, Stefanie
Daurer, Magdalena
Rabl, Roland
Chagnaud, Boris Philippe
Leopoldo, Marcello
Lacivita, Enza
Hutter-Paier, Birgit
Prokesch, Manuela
author_facet Sharghi, Shirin
Flunkert, Stefanie
Daurer, Magdalena
Rabl, Roland
Chagnaud, Boris Philippe
Leopoldo, Marcello
Lacivita, Enza
Hutter-Paier, Birgit
Prokesch, Manuela
author_sort Sharghi, Shirin
collection PubMed
description 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 5HT(7) 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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spelling pubmed-100979042023-04-14 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 Front Neurosci Neuroscience 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 5HT(7) 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. Frontiers Media S.A. 2023-03-30 /pmc/articles/PMC10097904/ /pubmed/37065917 http://dx.doi.org/10.3389/fnins.2023.1087788 Text en Copyright © 2023 Sharghi, Flunkert, Daurer, Rabl, Chagnaud, Leopoldo, Lacivita, Hutter-Paier and Prokesch. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Sharghi, Shirin
Flunkert, Stefanie
Daurer, Magdalena
Rabl, Roland
Chagnaud, Boris Philippe
Leopoldo, Marcello
Lacivita, Enza
Hutter-Paier, Birgit
Prokesch, Manuela
Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models
title Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models
title_full Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models
title_fullStr Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models
title_full_unstemmed Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models
title_short Evaluating the effect of R-Baclofen and LP-211 on autistic behavior of the BTBR and Fmr1-KO mouse models
title_sort evaluating the effect of r-baclofen and lp-211 on autistic behavior of the btbr and fmr1-ko mouse models
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097904/
https://www.ncbi.nlm.nih.gov/pubmed/37065917
http://dx.doi.org/10.3389/fnins.2023.1087788
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