Learning to perform instrumental tasks is an ability of all animals. In a population of rats, not all individuals will acquire an operant response for reward. We hypothesized that there could be a genetic explanation for differences between High Consumers (those that acquired the lever press response) and Low Consumers (lever press response is low). Additionally, we proposed that this genetic difference could produce measurable changes in response to novelty. Wistar rats were trained to lever press for a 0.2% saccharin reward and on the 10th day they were placed in a novel open field for 30 min to record locomotor activity. The prefrontal cortex and hippocampus were dissected and qPCR was used to measure mRNA expression. A significant difference (p = .048; 2-way ANOVA) in gene expression was observed between Low and High Consumers. A principal component analysis (PCA), to cluster which genes represent this difference, identified 4 genes; 5-HT2A and mGlu1 in the hippocampus and AMPA GluR1 and adrenergic α2A in the prefrontal cortex. Response to a novel open field also differed since Low Consumers displayed a higher Total Distance in comparison to High Consumers. Additionally, Low Consumers could be subdivided into Low-Lever (with lever press response only when water deprived) and Low-Non-Lever (lever press response is low throughout training). PCA with this subdivision identified an additional nine genes differing within the divisions; NMDA NR2B and GABAAα3 in the prefrontal cortex and adrenergic α2B and α2A, AMPA GluR1, GluR2 and GluR3, 5-HT1B and GABAAα5 in the hippocampus.