Nicotine abuse is the most critical but preventable public health problem. Although nicotinic acetylcholine receptor (nAChR) is identified as the main target of nicotinic signaling, the molecular and neuronal circuits of nicotinic signaling remain unknown. Using invertebrate models such as c. elegans or Drosophila metanogaster as animal models to study drug abuse has recently attracted the attention of researchers because of their simple nervous system, and the available powerful genetic tools in these models [Schafer WR, J. Neurosciences, 2002, Wolf FW and Heberlein U, Cur. Opp. in Neuroscience, 2003]. Utilizing a quantitative c. elegans behavior analysis system (Feng Z. et al, abstract in this meeting), a c. elegans locomotory acclimation behavior is identified and defined. Using this locomotory acclimation behavior as a behavioral assay, the c. elegans animals were found to response acutely to nicotine at a wild concentration range including concentrations close to physiological concentration in human blood after a cigarette consummation. This locomotory acclimation behavior is also found can be used in the study of nicotine adaptation, withdrawal, and possibly sensitization. The distinct roles of several nicotinic receptor subunits (
unc-29,
unc-38, and
unc-63), Go and Gq signaling circuits, and several neuronal transmitters (dopamine, serotonin, glutamate) in the locomotory acclimation behavior, and their functions in nicotinic signaling are discussed.