While it has been widely recognized that food restriction enhances learning and motivation, the neural mechanisms underlying this adaptation are not well defined. It is likely that changes in gene expression underlie the behavioral response to food restriction. Previously, microarray analysis was conducted on animals that had been food restricted (75% of normal caloric intake) over the course of five days (FR-5). Changes in gene expression were confirmed by quantitative PCR (qPCR) within the hypothalamus, as well as three brain regions within the meso-cortico-limbic circuitry including the medial prefrontal cortex (mPFC). The purpose of our experiments is to assess the role of the glucocorticoid receptor (GR) in mediating observed changes in gene expression, with a focus on Cdkn1a, Arrdc2, and Mertk. We hypothesized that similar molecular adaptations to FR-5 may also occur in peripheral tissue, and show that all three genes are up-regulated in the mouse kidney. We also hypothesized that some adaptations may occur in an acute restraint stress model and tested this by assessing gene expression in mice that were immobilized for 30 minutes. We found that Cdkn1a is up-regulated in the mPFC while Arrdc2 and Mertk are unchanged 2.5 hours after the stressor. Additionally, we show that Mertk is up-regulated in the male but not the female kidney, while Arrdc2 shows adaptation in both sexes (FR-5). In order to address whether these genes represent direct targets of the GR, we use bioinformatic approaches to identify relevant GBRs (glucocorticoid binding regions) and plan to use reporter assays in mammalian cells to assess whether they are functional GREs (glucocorticoid responsive elements). These ongoing studies will better characterize the transcriptional response to mild food restriction and will determine the generality of the response across stress models, tissue types and in males versus females. Ultimately, we anticipate that these studies will allow us to address the role of these molecular responses in mediating long-term behavioral changes after mild and chronic stress.