Domitor

All the mice used in this study were housed in a specific pathogen-free environment at the Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University. They were maintained at 22–24°C and 50–60% humidity with a 14-h light (07:00-21:00)/10-h dark cycle. For anesthesia, a combination of three drugs was administered: medetomidine (Domitor; Meiji Seika Pharma, Tokyo, Japan) at 0.3 mg/kg body weight, midazolam (Dormicum; Astellas, Tokyo, Japan) at 4 mg/kg body weight, and butorphanol (Betolfal; Meiji Seika Pharma, Tokyo, Japan) at 5 mg/kg body weight. The final volume was adjusted using physiological saline at a dosage of 10 ml/Kg. When euthanasia was deemed necessary, it was carried out using the cervical dislocation method by technically skilled personnel to ensure a humane and ethical procedure, in line with the guidelines set by the Institute of Laboratory Animals.

PSB1115 was purchased from Santa Cruz Biotechnology, Inc (Santa Cruz, CA). Methylcellulose, ibudilast and rolipram were obtained from Wako Pure Chemical Industries (Osaka, Japan). Medetomidine chloride (Domitor^®) and butorphanol tartrate (Vetorphale^®) were obtained from Meiji Seika Pharma Co., Ltd. (Tokyo, Japan) and midazolam was purchased from SANDOZ (Tokyo, Japan). Istradefylline and theophylline were purchased from Sigma (St. Louis, MO). Cilostazol and aminophylline were obtained from LKT laboratories, Inc. (St Paul, MN). MRS-1754 and BAY60-6583 were from Tocris Bioscience (Bristol, UK) and 1,3-dipropyl-8-cyclopentylxanthine (DCPCX), ZM241385 and CGS21680 were from Abcam (Cambridge, UK). ICR mice (5- or 6-week-old males, 28–33 g), primiparous late pregnant Wistar female rats and normal male Wistar rats (4- or 5-week-old, 150–250 g) were obtained from Charles River Laboratories Japan (Yokohama, Japan). The animals were housed under conditions of controlled temperature (22–24 °C) and illumination (12-h light cycle) conditions for 1 or 2 weeks before experiments. The experiments and procedures described here were performed in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health, and were approved by the Animal Care Committees of Keio University and St. Marianna University.