Amino acids are essential for almost all biological processes and many cannot be synthesized de novo. Thus, it is crucial that all animals, including humans, acquire an adequate amount of protein in their diet. Here, we show that rats maintained on a proteinrestricted diet develop a strong preference for protein, relative to carbohydrate. In addition, this preference was associated with increased neural activation in ventral tegmental area while rats were consuming protein. These changes were relatively persistent as when protein levels were restored by switching back to regular chow, behavioral preference and elevated neural activity to protein did not completely disappear. This study provides the first indication that activity in mesolimbic circuitry is involved in generating an appetite for protein in times of need.The artificial sweetener, saccharin, was used to familiarize rats with the retractable sippers in the behavioral chambers. Following five saccharin sessions, rats experienced four daily conditioning sessions in which they were given access to one bottle containing either distinctly-flavored casein (protein) or maltodextrin (carbohydrate) solutions, alternated from day to day ( Figure S2). For both solutions, rats licked more on the second session in which it