Antagonism of ketamine-xylazine anesthesia in rats by administration of yohimbine, tolazoline, or 4-aminopyridine

Abstract

SUMMARY Antagonism of ketamine-xylazine (85 mg of ketamine/ kg of body weight and 15 mg of xylazine/kg, im) anesthesia in rats by yohimbine (yoh; 1, 5, 10, and 20 mg/kg, ip), tolazoline (tol; 10, 20, or 50 mg/kg, ip), 4-aminopyridine (4-AP; 1 or 5 mg/kg, ip), or a combination of yohimbine and 4-aminopyridine (yoh:4-AP, 1 mg/kg: 1 mg/kg or 5 mg/kg: 1 mg/kg, ip) was studied. All dosages of yoh, tol, 4-AP, and yoh:4-AP reduced the time to appearance of corneal and pedal reflexes. Only tol was effective in reducing time to appearance of the crawl reflex and recovery time. Yohimbine, 4-AP, yoh:4-AP, and tol were effective in reversing respiratory depression caused by ketamine-xylazine anesthesia, but anesthetic-induced hypothermia was not antagonized. When given to nonanesthetized rats, the antagonists had little influence on respiratory rate, but all antagonists caused significant (P < 0.05) reduction in core body temperature for at least 90 minutes. When yoh was used as an anesthetic antagonist at dosage of 20 mg/kg, 20% mortality was observed and was attributable to acute respiratory arrest. The use of 4-AP and yoh:4-AP at the dosages studied induced moderate to severe muscular tremors. In conclusion, tol at dosage of 20 mg/kg given ip, appears to be an appropriate antagonist for ketamine-xylazine anesthesia in rats.