Associative learning deficiencies underlying aberrant feeding in the valproate rat model of autism

Abstract

Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental condition prevalent in over 1% of the global population. Aberrant feeding behaviours and feeding dysregulation are a prevalent and understudied difficulty. Individuals with ASD often present with poor health outcomes, including over/under eating, obesity, and restrictive feeding associated with poor dietary habits, however the underlying mechanisms are poorly understood. Here we propose an explanation for some neural mechanisms that may be responsible for feeding dysregulation present in ASD. We demonstrate that valproate rat models of ASD (VPA ASD) have a blunted neural response to LiCl-induced conditioned taste aversion and show transcriptional changes in the arcuate nucleus of the hypothalamus. Findings of this study also show that VPA ASD rats have significantly higher neural activation in the nucleus accumbens and the dorsal vagal complex in response to food, compared to controls. Our research suggests that some of the feeding abnormalities seen in people with ASD may stem from signalling deficiencies in brain areas involved in associative learning responses following ingestion of foods that cause malaise. Extremely restrictive feeding behaviours seen in ASD phenotypes may be caused by difficulties identifying foods that make them sick. These findings contribute to understanding neuromolecular drivers of anomalous feeding behaviours in people with ASD.