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Reward-Related Behavioral, Neurochemical and Electrophysiological Changes in a Rat Model of Autism Based on Prenatal Exposure to Valproic Acid.

Abstract：

:Prenatal exposure to the antiepileptic drug valproic acid (VPA) induces autism spectrum disorder (ASD) in humans and autistic-like behaviors in rodents, which makes it a good model to study the neural underpinnings of ASD. Rats prenatally exposed to VPA show profound deficits in the social domain. The altered social behavior displayed by VPA-exposed rats may be due to either a deficit in social reward processing or to a more general inability to properly understand and respond to social signals. To address this issue, we performed behavioral, electrophysiological and neurochemical experiments and tested the involvement of the brain reward system in the social dysfunctions displayed by rats prenatally exposed to VPA (500 mg/kg). We found that, compared to control animals, VPA-exposed rats showed reduced play responsiveness together with impaired sociability in the three-chamber test and altered social discrimination abilities. In addition, VPA-exposed rats showed altered expression of dopamine receptors together with inherent hyperexcitability of medium spiny neurons (MSNs) in the nucleus accumbens (NAc). However, when tested for socially-induced conditioned place preference, locomotor response to amphetamine and sucrose preference, control and VPA-exposed rats performed similarly, indicating normal responses to social, drug and food rewards. On the basis of the results obtained, we hypothesize that social dysfunctions displayed by VPA-exposed rats are more likely caused by alterations in cognitive aspects of the social interaction, such as the interpretation and reciprocation of social stimuli and/or the ability to adjust the social behavior of the individual to the changing circumstances in the social and physical environment, rather than to inability to enjoy the pleasurable aspects of the social interaction. The observed neurochemical and electrophysiological alterations in the NAc may contribute to the inability of VPA-exposed rats to process and respond to social cues, or, alternatively, represent a compensatory mechanism towards VPA-induced neurodevelopmental insults.

journal_name

Front Cell Neurosci

journal_title

Frontiers in cellular neuroscience

authors

Schiavi S,Iezzi D,Manduca A,Leone S,Melancia F,Carbone C,Petrella M,Mannaioni G,Masi A,Trezza V

doi

10.3389/fncel.2019.00479

subject

Has Abstract

pub_date

2019-10-25 00:00:00

pages

479

issn

1662-5102

journal_volume

pub_type

杂志文章

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Reward-Related Behavioral, Neurochemical and Electrophysiological Changes in a Rat Model of Autism Based on Prenatal Exposure to Valproic Acid.