Nicotine, the toxic substance that is exclusively absorbed from smoking, produces a wide array of behavior and collectively propels drug-seeking behaviors when abused. The neurotransmitter dopamine (DA) is important in the reward and reinforcing properties of many addictive drugs: however, the effect of nicotine by cigarette smoking itself on the expression of DA receptors in the caudate-putamen (CPu), nucleus accumbens (NAc) and olfactory tubercle (OTu) has not been elucidated completely. Hence, the effects of smoking and nicotine on DA receptors need to be defined. In this research, the effect of smoking and nicotine addiction on the DA D1 and D2 receptors in the rat CPu, NAc and OTu were studied. Adult male Spraque-Dawley (S.D., n=50) rats were administered with cigarette smoke (passive inhaled for 10 min and 1 h, 500 ml x 3 times/day, 4 weeks) and nicotine (oral, 3 mg/day). DA D1 and D2 receptor mRNA levels were determined by in situ hybridization and RNase protection assay (RPA). In the smoking groups (10 min and 1 h), DA D1 and D2 receptor mRNA greatly increased in the CPu and NAc, and most of all in the NAc. The nicotine treated group showed increased expression of DA D1 and D2 receptor mRNA too, but statistically less than in the smoking group. In the smoking group, DA D1 and D2 receptor mRNA levels were significantly higher in the CPu and NAc than in the nicotine group (P<.01). These results suggest that smoking and nicotine administration both influence DA receptor mRNAs in the CPu, NAc and OTu, in terms of up-regulation. The up-regulation was much more evident in the smoking group than in the nicotine group. In conclusion, we believe that smoking up-regulate the DA receptor mRNA expression significantly higher in rat CPu and NAc than nicotine but only a little bit higher in OTu.