AUTHOR=Sharghi Shirin , Flunkert Stefanie , Daurer Magdalena , Rabl Roland , Chagnaud Boris Philippe , Leopoldo Marcello , Lacivita Enza , Hutter-Paier Birgit , Prokesch Manuela 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1087788

DOI=10.3389/fnins.2023.1087788

ISSN=1662-453X

ABSTRACT=Abstract
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. The GABAB receptor agonist R-Baclofen and the selective agonist for the 5HT7 serotonin receptor agonist 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 and Fmr1-KO mice acutely with R-Baclofen or LP-211 and evaluated the behavior of animals in a series of tests. 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. 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.