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1- Experimental Pharmacology Laboratory, Neurobehavioral Research Laboratory, Department of Pharmacology, PGIMER, Chandigarh, India.
2- Experimental Pharmacology Laboratory, Neurobehavioral Research Laboratory, Department of Pharmacology, PGIMER, Chandigarh, India. Department of Neurology, PGIMER, Chandigarh, India.
Abstract:  
Background: Valproic acid is the most widely used chemical to develop the preclinical model of autism spectrum disorder (ASD). However, in addition to autism, it has different teratogenic effects like teeth malformation, tail kink, and abnormal body growth in offspring. However, no study has explored VPA-induced maternal behavior, miscarriage, and maternal Cannibalism. We aim to determine the cannibalistic effects of VPA in pregnant female Wistar rats and VPA's influence to cause miscarriage frequency.
Methods: Our study used pregnant Wistar rats. On GD 12.5, they were treated with VPA at 600 mg/kg i.p., dissolved in saline at 250 mg/ml concentration. The observations were mean litter size, mean male/female pups, mean mortality, maternal Cannibalism, mean pups alive, Cannibalism of malformed pups, miscarriage, survival analysis of pups, and odds and risk ratio were calculated for deaths observed in both (control & VPA-treated) the groups. The study was conducted till the weaning period.
Results: VPA-exposed pregnant females portrayed significantly decreased litter size (p<0.0001), significantly higher cannibalistic behavior (p=0.0023), and significantly higher cannibalism of malformed pups (p=0.0484) than the control group. VPA had caused complete pregnancy loss (miscarriage) in pregnant females (n=5). Moreover, the VPA group's mortality percentage (p=0.0019) was significantly higher than the control group.
Conclusion: Overall, VPA has marked teratogenic effects (anatomical and morphological changes in offspring) with maternal behavior disruption, which causes Cannibalism in Wistar female rats. The current manuscript findings can aid in investigating the novel mechanisms involved in maternal behavior disruption during the development of the VPA autism model.
Type of Study: Original | Subject: Behavioral Neuroscience
Received: 2022/06/30 | Accepted: 2022/08/9

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