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Psychopharmacology (Berl). 2013 Jun;227(3):393-402. doi: 10.1007/s00213-013-2979-y. Epub 2013 Jan 31.

Impaired social behavior in chicks exposed to sodium valproate during the last week of embryogenesis.

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  • 1Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Shiwa-gun, Iwate 028-3694, Japan.



To evaluate direct exposure to sodium valproate (VPA) during embryogenesis, we administered VPA to chick embryos and examined their social behaviors after hatching.


Embryos treated with VPA (35 μmol/egg) on day 14 were similar to controls for hatching date (day 21) and hatchlings' abilities, such as motor, imprinting, and surface righting. However, these VPA chicks on posthatching day 3 scored significantly low in the chick's social separation stress (SSS) test as follows. Aggregation test evaluated the speed of four chicks, individually isolated by a cardboard in a box, to aggregate upon removal of the cardboards. Belongingness test evaluated the speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner. Vocalization test for each chick was performed in an isolated corner by using a sound level meter. The results demonstrated that compared with controls, VPA chicks were significantly slow in aggregation (12.7 ± 2.5 s vs. 2.9 ± 0.9 s, p = 0.006) and belongingness (3.6 ± 0.28 s/40 cm vs. 2.6 ± 0.14 s/40 cm, P = 0.003) and weak in vocalization (13.4 ± 2.8 dB/30 s vs. 26.7 ± 1.3 dB/30 s, P = 0.001), respectively. Weight of cerebellum of VAP chick was 15 % lighter than controls (P = 0.004).


Chick embryos exposed to VPA during the last week of embryogenesis had impaired social behaviors in spite of normal mortar and imprinting ability. The present method will be a useful animal model for assessing the effects of environment during embryogenesis on social behaviors in later life.

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