A safe and reliable method for anesthetizing rats has long been a leading concern of biomedical researchers. We recently found that the intraperitoneal administration of propofol combined with medetomidine and fentanyl is safe for mouse anesthesia. Here we studied whether the same combination could be used for general anesthesia in rats. We used male Wistar rats to test 10 combinations of propofol, medetomidine, and fentanyl administered intraperitoneally and reversed with intraperitoneal atipamezole 30 min after induction. The depth of anesthesia, induction time, loss of pedal withdrawal reflex, pulse rate, and respiratory rate were evaluated, along with the duration and quality of induction, surgical anesthesia, and recovery. The combination of propofol and medetomidine provided a predictable induction and sufficient hypnosis and muscle relaxation, but surgical anesthesia (loss of pedal withdrawal reflex) was difficult to achieve with this protocol. The addition of fentanyl increased analgesia, making it possible to achieve surgical anesthesia. In conclusion, combination of propofol (100 mg/kg), medetomidine (0.1 mg/kg), and fentanyl (0.1 mg/kg) is a safe and practical technique for intraperitoneal anesthesia in rats, providing a surgical window of 25 min and restraint for 30 min, with rapid recovery after administration of atipamezole.
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