Effect of anesthetics and a convulsant on normal and mutant Caenorhabditis elegans

Abstract

The authors have developed a method for studying the action of volatile anesthetics in Caenorhabditis elegans (C.e.), a free living nematode. C.e. appears to be a useful model for the study of the influence of genetics on susceptibility to anesthetics. This worm has a small, completely defined nervous system, easily manipulated genetics, and a large number of nervous system mutants. Under normal conditions C.e. moves almost constantly. When exposed to anesthetics there is an initial phase of increased locomotion, followed by uncoordinated motion that progresses to immobility. Motion returns quickly when the nematodes are removed from the anesthetic. The authors called loss of locomotion 'anesthesia'. The ED50s of various anesthetics with C.e. are as follows: methoxyflurane 0.45%, chloroform 1.25%, halothane 2.7%, enflurane 4.2%, isoflurane 5.6%, fluroxene 9.9%. The authors also studied the action of a convulsant, flurothyl, on C.e. Flurothyl has anesthetizing properties in these animals with an ED50 of 8.1%. No convulsant activity was noted. However, mixtures of halothane and flurothyl were antagonistic in their effects, while halothane and enflurane were additive. Furthermore, the authors isolated a mutant strain (HS1) of C.e. that shows altered responses to several anesthetics and a convulsant. HS1 is uncoordinated when not exposed to anesthetics. Like the normal strain (N2) NS1 loses mobility when exposed to anesthetics. The ED50s for various anesthetics in HS1 were as follows: methoxyflurane 0.04%, chloroform 0.52%, halothane 0.85%, isoflurane 4.9%, enflurane 6.0%, fluroxene 10.9%. When compared with the normal C.e., HS1 exhibits a marked increase in sensitivity to methoxyflurane, chloroform, and halothane. No alterations in sensitivity to isoflurane or fluroxene were noted. HS1 exhibited decreased sensitivity to enflurane. HS1 reverts to normal motion when exposed to low concentrations of flurothyl and shows decreased sensitivity to the anesthetic effects of flurothyl with an ED50 of 11.8%. The slope of the curve of the log ED50 versus the log oil/gas partition coefficient is steeper in mutant than in normal nematodes.