Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder

• Published in: Autism research Vol. 10; no. 12; pp. 1929 - 1944
• Main Authors: Anshu, Kumari, Nair, Ajay Kumar, Kumaresan, U.D., Kutty, Bindu M., Srinath, Shoba, Laxmi, T. Rao
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-12-2017
• Subjects: 5‐choice serial reaction time task; Aberration; Animal models; Animals; attention; Attention - physiology; Autism; Autism Spectrum Disorder - physiopathology; Data processing; Disease Models, Animal; environmental risk factors; Exposure; Female; Gender aspects; Gender differences; Impulsive behavior; Information processing; Male; Mathematical models; Pregnancy; Prenatal experience; Prenatal Exposure Delayed Effects - physiopathology; prenatal valproic acid; Rats; Rats, Sprague-Dawley; Reaction Time; Reaction time task; Rodents; Sensorimotor system; Sex; Sex differences; Sexes; Valproic acid; Valproic Acid - administration & dosage; animal models; prenatal valproic acid; attention; environmental risk factors; 5-choice serial reaction time task; autism; sex differences
• ISSN: 1939-3792; 1939-3806
• DOI: 10.1002/aur.1852

Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5‐choice serial reaction time task (5‐CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5‐CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre‐attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017, 10: 1929–1944. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Lay Summary
We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex‐specific characteristics. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. Our work validates the use of the VPA model in the quest for evaluating suitable therapeutic targets for improving attentional performance.