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It is thought that the gravitational environment of space exploration alters the effects of anesthetics; however, no evidence has as yet been reported. In the present study, we sought to provide direct evidence showing that hypergravity exposure for 14 days increases anesthetic effects and to examine the possible causes.Sprague-Dawley rats were raised in a 3g environment for 14 days. On the day of the experiment, rats were brought out of 3g and rested at 1g for 1 to 2 hours before IV propofol infusion (20 mg/kg, for 5 minutes). Control rats were continuously raised in a 1g environment. The effects of propofol were compared between rats raised in 1g and 3g environment by measuring time taken to induce the burst suppression in an electroencephalogram, nadir of arterial blood pressure, and time taken for the appearance of the righting response to noxious electrical stimulations. The time course of plasma propofol concentrations was also examined. Experiments were also conducted on rats with vestibular lesions to examine whether the vestibular system participated in the observed results. All values were expressed as mean ± SD.In rats raised in 3g environment, the mean time to induce burst suppression in the electroencephalogram was earlier (195.7 ± 15.1 seconds, P = 0.00037), the nadir of mean arterial blood pressure was lower (75.0 ± 15.5 mm Hg, P = 0.019), and mean time for the righting response to appear was later (39.0 ± 8.4 minutes, P < 0.0001) than in rats raised in 1g environment (267.3 ± 29.4 seconds, 100.6 ± 9.1 mm Hg, and 22.0 ± 3.1 minutes, respectively). However, mean time to induce burst suppression and for the righting response to appear did not change in rats with vestibular lesions raised in 3g environment (275 ± 29.4 seconds, 108.7 ± 14.6 mm Hg, and 20.8 ± 2.8 minutes, P = 0.95, 0.73, and 0.98 vs sham-treated rats continuously raised in a 1g environment, respectively). There was no difference between groups in the time course assessment of plasma propofol concentrations.The results provide evidence that hypergravity exposure for 14 days increases the effects of propofol. It is suggested that the results were not caused by differences in plasma propofol concentrations but by increased sensitivity, which was mediated via the vestibular system.