Nicotine affects the sexes differently. However, the molecular-neural mechanisms underlying these differences have not been fully elucidated. This study examined the effects of acute nicotine exposure on the nervous system and behavior between the sexes in C.elegans. We used a WT and a mutant strain for the dopaminergic receptor Dop-R to examine the effects of nicotine. In males, but not in hermaphrodites, we found a significant difference after exposure to nicotine. In addition, this effect found in the WT strain was not observed in dop-1 mutant males. These results confirm a difference between the sexes in response to nicotine. In addition, these results also demonstrate that in C. elegans, dopamine receptors have a differential role in the mediation of motor hyperactivity in both sexes.