Effects of Progesterone on Isoflurane Requirement for Balance Disturbance and Loss of Righting Reflex in Male Mice

Introduction It has been known that progesterone has central effects, as measured by minimum alveolar concentration in various experimental settings. Previously, we showed that progesterone reduces the sevoflurane requirement for the loss of righting reflex (LORR) using male mice. However, the combination of progesterone and isoflurane has not been studied. Therefore, in this study, we compared the effect of progesterone on anesthetic requirements in a mouse model. Methods Male C57BL/6 mice were treated with either progesterone (75 mg/kg) + olive oil or only olive oil. Animals were studied in closed cylinders supplied with oxygen and isoflurane that rotated four times per minute. Balance disturbance and loss of the righting reflex were counted. The data were analyzed by using a multiple independent variable logistics regression model. Results The concentrations at the onset of balance disturbances, represented by the effective dose 50% (ED₅₀) and effective dose 95% (ED₉₅) of isoflurane, were 0.37% and 0.45% for the control group and 0.34% and 0.41% for the progesterone group, respectively. Similarly, the concentrations for loss of righting reflex (LORR), represented by ED₅₀ and ED₉₅, were 0.55% and 0.62% for the control group and 0.53% and 0.60% for the progesterone group, respectively. Subcutaneous injection of progesterone at a dose of 75 mg/kg significantly reduced the isoflurane requirement for both balance disturbance (p = 0.0022) and LORR (p = 0.0218). Conclusion We conclude that progesterone decreased isoflurane concentration for both balance disturbance and LORR.