Mice with a loss of function mutation in the CLOCK gene (ClockΔ19 mutant mice) exhibit mania symptoms similar to those observed in patients, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation (Roybal et al., 2007). This evidence concerns the gene CLOCK and major depressive disorder.