The next question is whether or not these mice show bipolar disorder—like phenotypes. At first, basic behavioral phenotypes were examined by a conventional test battery. No abnormalities were found for sensorimotor functions, or learning and memory. The only significant finding was enhanced startle response. Although we did not further pursue this phenotype because it is apparently unrelated to bipolar disorder, this phenotype is easy to test, and might be used for the assessment of drug effects.To further test bipolar disorder-related phenotypes, we recorded wheel-running activity for a long period of up to 2 months. Although there was no detectable fluctuation of wheel running activity in male mice, the activity level was significantly lower in Tg mice compared with wild-type mice. In addition, the mice had characteristic circadian activity rhythm. The mice continued to run after the light turned on in the morning, and they began to run before the light turned off in the evening. Although it is difficult to compare the behavior of nocturnal animals with that of diurnal humans, this might correspond to insomnia in humans.Furthermore, we applied a tricyclic antidepressant, amitriptyline, which often causes a manic switch in patients with bipolar disorder. As a result, some of the Tg mice showed a manic switch-like behavioral alteration.