*2.2. Animals*

Crl:CD1 (ICR) male mice, 6 weeks old, and C57BL/6J male mice, 7 months and 22 months old (Charles River Japan, Tokyo, Japan), were maintained at Kirin Company Ltd. Mice were maintained at room temperature (23 ± 1 ◦C) under a constant 12-h light/dark cycle (light period from 8:00 am to 8:00 pm) and were fed a standard rodent diet (CE-2 (Clea Japan, Tokyo, Japan)). Behavioral pharmacological tests were performed in a sound-isolated room with the same temperature and light/dark cycles. All efforts were made to minimize suffering. For euthanasia, mice were placed into a chamber filled with vapor of isoflurane (Wako, Osaka, Japan). All experiments were approved by the Animal Experiment Committee of Kirin Company Ltd and conducted in strict accordance with their guidelines in 2016.
