3.2. Effects of morphine or fentanyl on respiratory depression in βarr2−/− mice
According to previous reports and our experimental results, the subcutaneous injection dose of morphine was set to 50 mg/kg to replicate previous experiments aiming to suppress morphine-induced respiratory depression in knockout animals (Raehal, Walker & Bohn, 2005), and a fentanyl dose of 0.40 mg/kg was selected for transgenic animals.
The respiratory rate and minute ventilation tended to decrease after morphine administration in all three mouse groups, and there were no significant differences among the three genotypes (Fig 3a, d). Compared with the findings in the wild-type group, morphine-induced increases in the inspiratory time and expiratory time were significantly depressed in βarr2−/− animals 40–90 min after subcutaneous injection (Fig. 3b, c). The respiratory rate, inspiratory time, expiratory time, and minute ventilation peaked 10 min after subcutaneous fentanyl injection in all three groups. At this time, the respiratory depressant effect was strongest, and there were no statistical differences among the three genotypes (Fig 4). The inspiratory time and expiratory time were statistically different between the wild-type and βarr2−/− groups at 25 min after administration. It was demonstrated that although wild-type mice did not differ from transgenic animals regarding the intensity of respiratory depression, it was more difficult for wild-type animals to recover respiratory function after administration.