Neuromolecular basis of anomalous feeding behaviour in the valproate rat model of autism

Autism spectrum disorder (ASD), which affects circa 1% of the global population, is characterized by impairments in social communication, interaction, language disability, sensory anomalies, repetitive behaviours, and intellectual disability. Aberrant feeding behaviour is a common comorbidity of ASD. ASD individuals often demonstrate extreme food selectivity, refusal, dependence on few very particular food items, neophobia etc. which can lead to nutritional deficiencies affecting development. However, the underlying neurophysiological mechanisms of aberrant food intake in ASD are not well known. Prenatal exposure to the antiepileptic drug, valproic acid (VPA), leads to autism. The prenatally VPA-exposed rats are model organisms to study ASD and they show ASD-like symptoms of, among others, elevated anxiety and decreased social interaction. Importantly, very little is known about appetite control in these animals. The overall goal of the studies included in this thesis was to identify potential feeding behavioural anomalies and associated neuromolecular changes in the VPA rat model of ASD. We thus hypothesize that ASD is associated with abnormal appetite and reward-driven feeding. The key factors shaping consumption involve hunger (determines search for calories), satiation (underpins termination of feeding) and reward (consumption for the 'pleasantness' of food, regardless of the energy requirements). Thus, in the first Specific Aim of this thesis, the hunger processing in the VPA animals was investigated. The ad libitum intake of ‘bland’ standard laboratory chow was assessed in VPA versus non-VPA controls maintained continuously on this diet. The adult VPA rats ate less ‘bland’ chow than healthy controls did, and it was coupled with a moderately lower body weight than that of the controls. VPA rats also ate less of the standard chow after acute food deprivation. There was an aberrant change in c-Fos immunoreactivity in key brain sites that govern food intake, inclu