Reward-related behaviour exhibits a recurring pattern with a period of about 24 hours and hence is circadian. This indicates potential interactions between the circadian and the reward systems in the brain. First evidence for an involvement of circadian clock-associated genes in drug-related reward behaviour came from studies in Drosophila, which showed that cocaine sensitization is dependent on clock gene expression. Subsequently, we found that mice lacking the Per1 or the Per2 genes showed abnormal sensitization and conditioned preference to cocaine. To find a molecular link between the clock and the reward system, we studied genes coding for key enzymes in dopamine metabolism. We found that the gene of the dopamine degrading enzyme monoamine oxidase A (MaoA) is regulated by clock components. A mutation in the clock gene Per2 leads to decreased expression and activity of MaoA in the mesolimbic dopaminergic system of the brain. As a consequence we find increased levels of dopamine leading to a depression-resistant like phenotype in Per2 mutant mice.