Clin Psychopharmacol Neurosci.  2016 Nov;14(4):338-344. 10.9758/cpn.2016.14.4.338.

Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats

  • 1Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon, Korea.
  • 2Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea.
  • 3Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, USA.
  • 4Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA.


OBJECTIVE: We reported that postnatal exposure of rats to valproic acid (VPA) stimulated proliferation of glial precursors during cortical gliogenesis. However, there are no reports whether enhanced postnatal gliogenesis affects behaviors related to neuropsychiatric disorders.
After VPA treatment during the postnatal day (PND) 2 to PND 4, four behavioral test, such as open field locomotor test, elevated plus maze test, three-chamber social interaction test, and passive avoidance test, were performed at PND 21 or 22.
VPA treated rats showed significant hyperactive behavior in the open field locomotor test (p<0.05). Moreover, the velocity of movement in the VPA group was increased by 69.5% (p<0.01). In the elevated plus maze test, VPA exposed rats expressed significantly lower percentage of time spent on and of entries into open arms more than the control group (p<0.05). Also, both sociability and social preference indices with strangers in the three-chamber social interaction test were significantly lower in the VPA exposed rats (p<0.05).
Our results suggest that altered glial cell development is another locus at which pathogenetic factors can operate to contribute to the neurodevelopmental disorder.


Valproic acid; Postnatal gliogenesis; Social behavior; Anxiety; Autistic disorder
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