BEHAVIORAL-EFFECTS OF VOLATILE ANESTHETICS IN CAENORHABDITIS-ELEGANS

Background: The nematode Caenorbabditis elegans offers many advantages as a model organism for studying volatile anesthetic action It has a simple, web-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 concentra tions and with an unusually slow time course. Here other behavioral dy sfunctions are considered as anesthetic endpoints in C. elegans. Metho ds: The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response da ta. Other volatile anesthetics were also tested for some behaviors. Es tablished protocols were used for behavioral endpoints that, except fo r pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposur e 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 inhib ition 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, halo thane produced immobility with a median effective concentration of 3.6 5 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halot hane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after ex posure to 1 vol% halothane but was significantly reduced after exposur e to immobilizing concentrations. Conclusions: Volatile anesthetics se lectively disrupt C. elegans behavior. The potency, time course, and r ecovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nerv ous system molecules may express structural moths similar to those on vertebrate anesthetic targets.