Measuring the Anesthetic Response to Chloroform and Isoflurane in General Anesthesia Mutants in Drosophila melanogaster

Objectives: Comparative analyses of anesthetic agents on mutants with altered anesthetic sensitivity remain limited in the current literature. This study examines the sensitivity of various Drosophila melanogaster wild-type strains and mutants to the volatile anesthetics chloroform and isoflurane. We utilized recently identified mutants in ion channel-encoding genes and others historically selected for anesthetic resistance, such as AGAR (autosomal general anesthesia resistant) and har (halothane-resistant). Method: Based on the principles of the conventional inebriometer assay used to isolate these mutants, we developed a new, simpler method to measure the anesthetic response in these flies. Results: Interestingly, we discovered that wild-type flies exhibit varying levels of anesthetic resistance. Contrary to previous reports, AGAR and har mutants showed little resistance to anesthesia using our method. Several ion channel mutants displayed increased resistance or sensitivity. Across all strains, isoflurane was more potent than chloroform. To ensure objectivity, all experiments were conducted double-blind. These findings highlight the variability in anesthetic sensitivity among both wild-type and mutant flies and underscore the importance of assay design in assessing resistance.