Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy
Abstract
Autism is a highly debilitating disorder that has recently displayed a dramatic rise in incidence. In order to realistically study preventative and remedial strategies, it is important that we develop and understand useful animal models of the disorder. The purpose of this study was to investigate the efficacy of the prenatal valproic acid (VPA) rat model of autism by examining the neuro-anatomical and behavioural outcomes of offspring exposed to this paradigm. The VPA-treated rats exhibited behavioural changes in the delayed non-match-to-sample task, novel object recognition, activity box, and Whishaw tray reaching task. Anatomically, there was a reduction in brain weight and cortical thickness, along with decreased dendritic branching in the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), and decreased spine density in the mPFC, OFC, and cerebellum. Behavioural and anatomical findings from this study produced reliable results indicating that prenatal VPA exposure may be a viable model for the study of autism in rats.
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Acute high-dose VPA exposure reduces cortical thickness, whereas chronic low-dose exposure increases cortical thickness.
“Acute exposure at a high dose reduces cortical thickness [250], whereas chronic exposure to a low dose increases cortical thickness [307].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [250]
Higher dose VPA exposure in rodents results in reduced brain weight, whereas lower dose does not affect brain weight.
“Exposure to a higher dose of VPA in rodents results in reduced brain weight [250, 265], whereas a lower dose does not affect brain weight [331].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [250]
In prenatal VPA models, spine density is reduced in the PFC, orbital PFC, cerebellum, and dorsal hippocampus, but increased in the ventral hippocampus, basolateral amygdala, and nucleus accumbens.
“Spine density is reduced in the PFC [42, 250, 297], orbital PFC [250, 297], cerebellum [250], and in the dorsal hippocampus [42, 346], but increased in the ventral hippocampus, basolateral amygdala and nucleus accumbens [42].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [250]
In prenatal VPA models, reduced dendritic branching but not length in the orbital PFC was reported in one study, whereas another showed decreased dendritic length in the same brain region.
“Reduced dendritic branching but not length in the orbital PFC was reported in one study [297], whereas another showed decreased dendritic length in the same brain region [250].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [250]
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- Authors
- Mychasiuk, R., Richards, S., Nakahashi, A., Kolb, B., & Gibb, R.
- Affiliations
- University of Lethbridge (CA)
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 2012
- Volume
- 34
- Issue
- 2-3
- Pages
- 268-276
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- OpenAlex
- W2077741292
- Cited by
- 82
- References
- 31
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- valproic acid, prenatal drug exposure, autism spectrum disorder, animal models of autism, rat offspring, behavioural deficits, neuroanatomy, dendritic branching, spine density, cortical thickness, orbitofrontal cortex, medial prefrontal cortex, cerebellum, novel object recognition
- MeSH terms
- Animals, Behavior, Animal, Brain, Female, Male, Neurons, Pregnancy, Prenatal Exposure Delayed Effects, Valproic Acid, GABA Agents, Maze Learning, Recognition, Psychology, Dendritic Spines, Rats
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