Increased volatile anesthetic requirement in short-sleeping drosophila mutants

Abstract

BACKGROUND: Anesthesia and sleep share physiologic and behavioral similarities. The anesthetic requirement of the recently identified Drosophila mutant minisleeper and other Drosophila mutants was investigated. METHODS: Sleep and wakefulness were determined by measuring activity of individual wild-type and mutant flies. Based on the response of the flies at different concentrations of the volatile anesthetics isoflurane and sevoflurane, concentration-response curves were generated and EC50 values were calculated. RESULTS: The average amount of daily sleep in wild-type Drosophila (n ≤ 64) was 965 ± 15 min, and 1,022 ± 29 in Na[har](P > 0.05; n ≤ 32) (mean ± SEM, all P compared to wild-type and other shaker alleles). Sh flies slept 584 ± 13 min (n ≤ 64, P < 0.01), Sh flies 412 ± 22 min (n ≤ 32, P < 0.01), and Sh flies 782 ± 25 min (n ≤ 32, P < 0.01). The EC50 values for isoflurane were 0.706 (95% CI 0.649 to 0.764, n ≤ 661) and for sevoflurane 1.298 (1.180 to 1.416, n ≤ 522) in wild-type Drosophila; 1.599 (1.527 to 1.671, n ≤ 308) and 2.329 (2.177 to 2.482, n ≤ 282) in Sh, 1.306 (1.212 to 1.400, n ≤ 393) and 2.013 (1.868 to 2.158, n ≤ 550) in Sh, 0.957 (0.860 to 1.054, n ≤ 297) and 1.619 (1.508 to 1.731, n ≤ 386) in Sh, and 0.6154 (0.581 to 0.649, n ≤ 360; P < 0.05) and 0.9339 (0.823 to 1.041, n ≤ 274) in Na[har], respectively (all P < 0.01). CONCLUSIONS: A single-gene mutation in Drosophila that causes an extreme reduction in daily sleep is responsible for a significant increase in the requirement of volatile anesthetics. This suggests that a single gene mutation affects both sleep behavior and anesthesia and sedation. © 2009, the American Society of Anesthesiologists, Inc.