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.