Nicotine has been reported to exert several biological and pharmacological activities in central nervous system. There are many studies on the relationship between dopaminergic neurons and nicotine dependence. However, the relevance between nicotine and serotonergic neurons on dependence remains unknown. We demonstrate here that the effect of continuous low dose nicotine administration on setoronergic neurons (5-HT) immunoreactive fibers and terminals were increased in nicotine (0.5 mg/kg/day, 28 days) treated rat forebrain including anterior cingulate cortex and hippocampus. These results indicate that low dose nicotine, levels of smoking, may be related the developing the dependence of nicotine via the changes of 5-HT neurons in forebrain.