Table 5.

VPA and autistic-like behavior in rodents.

Authors, Ref Number	Animals, Dose of VPA and Day of Treatment	Behavioral Outcome
Schneider, [148]	Pregnant Wistar rats; single intraperitoneal injection of 600 mg/kg VPA on 12.5 day of gestation.	ASD-like behavior appeared in VPA-exposed offspring at adolescence: lower sensitivity to pain, locomotor and stereotypic-like hyperactivity and exploratory activity and decreased social behaviors.
Win-Shwe, [149]	Pregnant Sprague-Dawley rats; intraperitoneal injection of 600 mg/kg of VPA on day 12.5 of gestation.	ASD-like behavior appeared in both adult male and female offspring: impaired sociability and impaired preference for social novelty.
Kawada et al. [150]	Pregnant ICR mice; intraperitoneal injection of 500 mg/kg VPA on day 9.5 of gestation.	ASD-like behavior: increased anxiety, reduced exploratory behavior and decreased social communication ability
Dos Santos et al. [151]	Pregnant BALB/C mice; intraperitoneal injection (IP) of 600 mg/kg VPA on day 12.5 of gestation.	ASD-like behavior in 5-month-old male and female offspring. Abnormal behavior in exploring novel environments and assessing risk. Higher impairment in females.
Chaliha et al. [144]	A systematic review of the literature exploring VPA’s effect on the presentation of ASD-like behavioral changes in rodents.	Main core ASD-like behaviors were defined: Social Impairment Repetitive Behaviors Cognitive Rigidity
Fereshetyan et al. [147]	Pregnant Sprague–Dawley rats; prenatally exposed to single IP injection with 500 mg/kg VPA at embryonic 12.5 day. Pups received 200 mg/kg of VPA on postnatal days 5–12. A battery of different behavioral tests was performed on PND30–40 (adolescence) and PND60–70 (adulthood).	ASD-like behavior detected in either prenatally or postnatally VPA-treated offspring: passive playing behavior, low preference for social interaction, increased repetitive behavior, locomotor hyperactivity, low exploratory activity and decreased anxiety. Behavioral changes were greater in adolescent rats than at adulthood.
Ornoy et al. [152]	Review: sex-related changes in the clinical presentation of ASD in children and in animal models of ASD-like behavior.	Behavioral, electrophysiologic and molecular sex-related differences found in genetic and non-genetic experimental animal models of ASD-like behavior.
Ornoy et al. [153]	Prenatal and early postnatal administration of a single dose of VPA 300 mg/Kg injected IP to ICR mice.	Prenatal and postnatal VPA-exposed offspring of both sexes had ASD-like behavior: more repetitive movements, higher anxiety and reduced memory in females. Reduced sociability, decreased working memory and normal locomotion in males.
Kotajima-Murakami et al. [159]	Subcutaneous injections of 600 mg/kg VPA to pregnant mice on gestational day 12.5.	ASD-like behavior: decreased social interaction.
Rodier et al. [155]	Pregnant rats; single IP injection of 350 mg/kg VPA on days 11.5–12.5 of pregnancy.	Reduced number of neurons in motor nuclei of cranial nerves within the brainstem.
Ingram et al. [156]	Pregnant rats; IP injected with 600 mg/kg VPA on day 12.5 of gestation.	Reduction in the size of the cerebellar hemispheres; reduction in the number of Purkinje cells.
Zhao et al. [160]	Cynomolgus monkeys (Macaca fascicularis), treated prenatally with 200 or 300 mg/kg VPA on gestational days 26 and 29.	ASD-like behavior: impaired social interaction, repetitive movements and more attention on nonsocial stimuli by eye tracking analysis.