Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C082

Oral Communications

Assesing Empathy in Valproic Acid Induced Autism Model of Rats

S. Tunçak1,2, B. Goren1, P. Oz3,4

1. Medicine- Physiology, Uludag University, Bursa, Turkey. 2. Psychology, Uskudar University, Istanbul, Turkey. 3. Molecular Biology and Genetics, Uskudar University, Istanbul, Turkey. 4. Neuropsychopharmacology Application and Research Center, Uskudar University, Istanbul, Turkey.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with genetic, neurobiological and environmental roots. This complex disorder has a variety of symptoms from social interaction, communication and empathy deficits to repetitive and stereotyped behavior (1). Animal models play a key role to understand symptoms and mechanism of ASD. Prenatal exposure to valproic acid (VPA) increases the risk of ASD in humans and autism-like symptoms in rodents (2). VPA model of ASD is widely used, however empathy deficits has not been studied with this method yet. Wistar Albino pregnant females used in this study were grouped to receive either single 400 mg/kg VPA dissolved in saline (n=3) or same volume of saline (control, n=2) intraperitoneally on embryonic day 12.5. On postnatal day 21 (P21) rats were separated from mother and caged in with same sex siblings. Rats were tested for empathy on P30 and P60 in a 25x60x30 cm Plexiglas box. The set up includes a familiar rat from the same cage of subject rat where familiar rat is in a restrainer at the centre of the box. Subject rat, then, was placed in the box and its behavior was observed for 10 minutes. To measure acute empathy and avoid effects of learning, pups were not trained before the test and were not given any reinforcements or punishments. Besides testing for empathy, rats were tested for olfactory discrimination, social recognition, social preference, pre-pulse inhibition, locomotor activity and marble burying for validation of the VPA model. To assess empathy, the socially attentive time of the subject rat with the familiar was measured and subject's tendency to free the restrained rat was calculated by the frequency of attempt to remove the restraining block. Both values were analyzed with one-way ANOVA and Tukey-Kramer post hoc test. For attentive behavior, control females (CF) (n=15) showed higher values than VPA females (VF) (n=9) on both P30 and P60 (p<0.01; p<0.01). On the other hand, control males (CM) (n=7) showed significantly higher values than VPA males (VM) (n=17) on P60 only (p<0.01). Total control and VPA values differed on P30 and P60 (p<0.01; p<0.01). Escape attempt frequencies of CF-VF and CM-VM on P30 showed no differences where as on P60 values of CF over VF and CM over VM were higher (p<0.01; p<0.05). Total control values were higher than VPA on P30 and P60 (p<0.05; p<0.01). Our results suggest that empathetic behavior in VPA group pups is disrupted compared to controls. Elevation of values on P60 implies that measured behavior improves over time and present in females from earlier days. As a conclusion, VPA-induced model of ASD shows promising data to model empathy defects, thus, gives us an insight on biopyschosocial aspects of ASD.

Where applicable, experiments conform with Society ethical requirements