Comparison of valproic acid-induced autism spectrum disorder models between SD rats and C57 mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To compare the difference and similaritiy in growth, neurodevelopment and neurobehavioral characteristics between SD rat and C57 mouse models of valproic acid (VPA)induced autism spectrum disorder (ASD), and select an appropriate experimental species for the study of ASD. METHODS SD rats or C57 mice were ip given VPA 600 mg·kg-1 on embryonic day 12.5 of gestation (VPA groups) or an equal dosage of saline (normal control group). The farrowing rate of pregnant rats or mice and 4-day survival rate were observed. The male pups' malformation rate, body mass, tail length, incisor eruption, eye opening and development of fur were detected to observe physiological development. The neurodevelopment was measured in male pups including the number of days taken by surfacing righting reflex, cliff avoidance reflex, air righting reflex, pivoting, crawling and bar holding test and auditory startle to become positive. In addition, three chamber sociability test, open-field test and self-grooming test were used to assess autistic-like behaviors. RESULTS Compared with C57 mice in normal control group, the VPA groups presented a low farrowing rate in pregnant mice (P<0.05), and high external abnormality in new born offspring (P<0.01). However, there was no significant difference between SD rats in normal control group and those in VPA group. Compared with C57 mice in normal control group, the 4-day survival rate of offspring of the VPA group was significantly reduced (P<0.05), but there was no significant difference between SD rats in normal control group and those in VPA group. The male offspring of C57 mice in VPA group showed significant growth retardation compared with the normal control group, such as lower body mass at 20 and 25 d after birth (P<0.05), delayed incisor eruption (P<0.05) and eye opening (P<0.01). Although the body mass of the male offspring SD rats in VPA group was also significantly lower than that of normal control group at the same time points (P<0.01), there was no significant delay in the incisor eruption or eye opening. Compared with the male offspring of SD rats in normal control group, the VPA group had a significant delay in surface righting reflex (PO.01), cliff avoidance reflex (P<0.01), air righting reflex (P<0.05), crawling (P< 0.01) and bar holding test (P<0.01). Compared with the normal control group, pivoting (P<0.05) and bar holding test (P<0.05) in the C57 mice VPA group were delayed. In the three chamber sociability test, open field test and self-grooming test, the male offspring of SD rats in VPA group showed decreased spatial exploration ability (P<0.01), impaired social preference and novelty preference (P<0.01), and repetitive and stereotyped behaviors (P<0.05). VPA mice only exhibited reductions in spatial exploration ability and novelty preference (P<0.05). CONCLUSION If SD rats and C57 mice are exposed to VPA in the second trimester of pregnancy, their male offspring exhibits behavioral abnormalities relevant to ASD. However, SD rats are superior to C57 mice in building ASD animal models in terms of maternal pregnancy condition, cost and model face validity.