<p>Novelty has significant effects on feeding behavior. New foods and unfamiliar environments suppress consumption, and adaptation to novelty is fundamental to survival. Yet, little is known about habituation to eating in a novel environment. The aim of the current study was to determine if context familiarity impacts habituation to novel food and to identify underlying neural substrates. Adult male and female rats were tested for consumption of a novel, palatable food in a novel or familiar environment across four habituation sessions and a final test session. Test-induced Fos expression was measured in amygdalar, thalamic, prefrontal, and hippocampal regions known to be recruited during the first exposure to novelty. Rats in the novel context ate less compared to rats in the familiar context during each habituation session and test, and females ate less than males during the first session. Habituation to eating in the novel context robustly induced Fos in the majority of regions analyzed, including the central, basolateral, and basomedial nuclei of the amygdala, thalamic paraventricular and reuniens nuclei, and the hippocampal field CA1. Females had overall higher Fos induction in most regions analyzed and higher in the novel condition in the reuniens nucleus. Bivariate correlation analyses of Fos induction between regions found a large number of correlations in the novel context condition. Females tested in the novel context had uniquely large number of correlations between all regions analyzed, except for one thalamic subregion. These results suggest that novelty from context remains relevant late in habituation and recruits a distinct and more interactive network in females than in males.</p>