Behavioral effects of volatile anesthetics in Caenorhabditis elegans.
BACKGROUND
The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans.


METHODS
The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C.


RESULTS
The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations.


CONCLUSIONS
Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.
Crowder
C M
CM
Department of Anesthesiology, Washington University School of Medicine, Saint Louis, Missouri, USA. crowderm@morpheus.wustl.edu
Shebester
L D
LD
Schedl
T
T
D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D018685:Anesthetics, Inhalation; D006221:Halothane