Abstract: Objective: To examine brain dopamine expression in chronic high-fat diet(HFD)-induced obese mice.Methods: Ten male mice were fed by a high-fat diet (HF:45% of calories from fat) for 12 weeks and then classified as HFD group. Ten male mice were fed a low-fat diet (LF:10% of calories from fat) and used as control group (NCD). In the 10^th week, the blood of the caudal vein was collected to determine the basal blood glucose level after both groups mice were fast for 12 h. Intraperitoneal (IP) glucose tolerance test (GTT) and insulin tolerance (ITT) were performed in HFD and NCD mice in the 12^th week. Animals were sacrificed after fasting for 4 hours at the 12^th week. Brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry.Results: After 12 weeks of feeding, body weight was significant higher in HFD mice than that in NCD ones. During GTT and ITT, HFD mice had significantly decreased glucose tolerance and insulin tolerance at 15 min and 30 min respectively than NCD ones (P<0.05). There were higher plasma insulin concentration and leptin concentration in HFD mice than those in NCD ones (P<0.05). High fat-induced increased body weight was associated with increased cellular activation, indicated by Fos immunoreactive (ir) staining, in nucleus accumbens(NAcc), paraventricular nucleus (PVN), ventral tegmental area (VTA) and substantia nigra (SN) than those of NCD ones (P<0.05); and also significantly associated with enhanced in the number of cells labeled for tyrosine hydroxylase (TH-ir), and the number of cells co-labeled for TH-ir/Fos-ir in the VTA and SN than those of NCD ones (P<0.01). Moreover, there was significantly relationship TH-ir positive cell numbers with final body weight in VTA and SN in HFD mice (P<0.05).Conclusion: The results showed that chronic consumption of high-fat food was associated with plasticity-related changes in reward circuitry in mice.

Key words: high fat diet, obesity, immediate-early c-fos, tyrosine hydroxylase