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The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid

There is still no effective treatment that addresses the core symptoms of autism spectrum disorders (ASD), including social and communication deficits. A comprehensive body of evidence points to the cholinergic system, including alpha7–nicotinic acetylcholine receptors (α7–nAChRs), as a potential ta...

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Autores principales: Gzielo, Kinga, Nikiforuk, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697996/
https://www.ncbi.nlm.nih.gov/pubmed/36422547
http://dx.doi.org/10.3390/ph15111417
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author Gzielo, Kinga
Nikiforuk, Agnieszka
author_facet Gzielo, Kinga
Nikiforuk, Agnieszka
author_sort Gzielo, Kinga
collection PubMed
description There is still no effective treatment that addresses the core symptoms of autism spectrum disorders (ASD), including social and communication deficits. A comprehensive body of evidence points to the cholinergic system, including alpha7–nicotinic acetylcholine receptors (α7–nAChRs), as a potential target of pharmacotherapy. A promising approach is based on positive allosteric modulators (PAMs) of these receptors due to their advantages over direct agonists. Nevertheless, α7 n–AChR ligands have not been widely studied in the context of autism. Therefore, using one of the most widely used rodent models of ASD, that is, prenatal exposure to valproic acid (VPA), we examined the impact of α7–nAChR PAMs (PNU–120596 and CCMI) on socio-communicative behavior during social play in adolescent male and female rats. The current study demonstrated that PAM treatment affected certain aspects of socio-communicative behavior in adolescent rats. Accordingly, PNU–120596 ameliorated deficient play abilities in VPA-exposed males, as revealed by increased play time during a social encounter. In addition, this compound enhanced the emission of ultrasonic vocalizations that accompanied playful interactions. Moreover, we observed the overall effect of PNU–120596 on non-playful forms of social behavior (i.e., social exploration) and acoustic parameters (i.e., the duration) of emitted calls. The present results suggest the ability of α7–nAChR PAMs to facilitate socio-communicative behavior in adolescent rats.
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spelling pubmed-96979962022-11-26 The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid Gzielo, Kinga Nikiforuk, Agnieszka Pharmaceuticals (Basel) Communication There is still no effective treatment that addresses the core symptoms of autism spectrum disorders (ASD), including social and communication deficits. A comprehensive body of evidence points to the cholinergic system, including alpha7–nicotinic acetylcholine receptors (α7–nAChRs), as a potential target of pharmacotherapy. A promising approach is based on positive allosteric modulators (PAMs) of these receptors due to their advantages over direct agonists. Nevertheless, α7 n–AChR ligands have not been widely studied in the context of autism. Therefore, using one of the most widely used rodent models of ASD, that is, prenatal exposure to valproic acid (VPA), we examined the impact of α7–nAChR PAMs (PNU–120596 and CCMI) on socio-communicative behavior during social play in adolescent male and female rats. The current study demonstrated that PAM treatment affected certain aspects of socio-communicative behavior in adolescent rats. Accordingly, PNU–120596 ameliorated deficient play abilities in VPA-exposed males, as revealed by increased play time during a social encounter. In addition, this compound enhanced the emission of ultrasonic vocalizations that accompanied playful interactions. Moreover, we observed the overall effect of PNU–120596 on non-playful forms of social behavior (i.e., social exploration) and acoustic parameters (i.e., the duration) of emitted calls. The present results suggest the ability of α7–nAChR PAMs to facilitate socio-communicative behavior in adolescent rats. MDPI 2022-11-16 /pmc/articles/PMC9697996/ /pubmed/36422547 http://dx.doi.org/10.3390/ph15111417 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Gzielo, Kinga
Nikiforuk, Agnieszka
The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
title The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
title_full The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
title_fullStr The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
title_full_unstemmed The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
title_short The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
title_sort effects of positive allosteric modulators of α7–nachr on social play behavior in adolescent rats prenatally exposed to valproic acid
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697996/
https://www.ncbi.nlm.nih.gov/pubmed/36422547
http://dx.doi.org/10.3390/ph15111417
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