Long-lasting behavioral and neuroanatomical effects of postnatal valproic acid treatment.

Publication date: Feb 26, 2020

Valproic acid (VPA) administered to mice during the early postnatal period causes social, cognitive, and motor deficits similar to those observed in humans with autism spectrum disorder (ASD). However, previous studies on the effects of early exposure to VPA have largely focused on behavioral deficits occurring before or during the juvenile period of life. Given that ASD is a life-long condition, the present study sought to extend our understanding of the behavioral profile following early postnatal VPA into adulthood. Male mice treated with VPA on postnatal day 14 (P14) displayed increased aggression, decreased avoidance of the open arms in the elevated plus maze, and impaired reversal learning in the Y maze. This may indicate a disinhibited or impulsive phenotype in male, but not female, mice treated with VPA during the second week of postnatal life. Decreased dendritic spine density and dendritic spine morphological abnormalities in the mPFC of VPA-treated mice may be indicative of PFC hypofunction, consistent with the observed behavioral differences. Since these types of long-lasting deficits are not exclusively found in ASD, early life exposure to VPA may reflect dysfunction of a neurobiological domain common to several developmental disorders, including ASD, ADHD, and conduct disorder.

Norton, S.A., Gifford, J.J., Pawlak, A.P., Derbaly, A., Sherman, S.L., Zhang, H., Wagner, G.C., and Kusnecov, A.W. Long-lasting behavioral and neuroanatomical effects of postnatal valproic acid treatment. 15363. 2020 Neuroscience.

Concepts Keywords
ADHD Developmental disorder
Autism Spectrum Disorder Valproate
Cognitive Autism spectrum
Conduct Disorder Developmental psychology
Dendritic Spine Developmental neuroscience
Disinhibited Learning disabilities
Indicative RTT
Maze Organ systems
Morphological Neuroscience
Neuroanatomical Psychiatry
Neurobiological Psychiatric diagnosis
Open Arms Dysfunction
Phenotype Common developmental disorders
Valproic Acid


Type Source Name
disease MESH impulsivity
disease MESH conduct disorder
disease MESH abnormalities
drug DRUGBANK Valproic Acid
disease MESH autism spectrum disorder

Original Article

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