Ethanol and general anesthetics are widely used drugs, but the mechanism of action of these compounds has remained uncertain despite intensive study. Biochemical and electrophysiological experiments have shown that these compounds alter the function of a large variety of receptors, ion channels, transporters and second messenger systems at physiological concentrations. Yet, the contribution of any of these potential targets to the intoxicating or behavioral effects of the drugs is unclear. Unbiased forward genetic screens for resistant or hypersensitive mutants represent an attractive means of identifying the relevant molecular targets or biochemical pathways mediating the behavioral effects of neuroactive compounds.
C. elegans has proven to be a particularly useful system for such studies. The behavioral effects of ethanol and certain general anesthetics occur at equivalent tissue concentrations in mammals and in C. elegans, suggesting the existence of conserved drug targets in the nervous system.
This chapter reviews the results of studies directed toward determining the mechanisms of action of ethanol and general anesthetics. Studies of the neural adaptations that occur with prolonged drug exposure are also discussed. The methods used to characterize the actions of ethanol and anesthetics should be applicable to the characterizations of other compounds that affect the behavior of C. elegans.
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