Figure 7.
Clofibrate blocked nicotine-induced elevations of extracellular dopamine in the nucleus accumbens shell. Microdialysis was performed in awake, freely moving rats. Nicotine (‘Nic' 0.4 mg/kg, intravenously) significantly increased dopamine (‘DA') levels, but this effect was significantly blocked by treatment with 300 mg/kg clofibrate (‘Clof'). Administration of the PPAR-α antagonist MK886 (‘MK' 3 mg/kg, intraperitoneally) 20 min before clofibrate reversed the effects of clofibrate. (a) Dopamine levels (expressed as a percentage of basal level) over time in rats treated with MK886 or its vehicle, followed by clofibrate (‘Clof') or its vehicle, and finally by nicotine (‘Nic') or saline (‘Sal'). Arrows indicate times of drug or vehicle (‘Veh') administration. (b) Dopamine levels for the same four conditions, expressed as area under the curve (‘AUC', relative to the mean level in the ‘Veh+Veh+Nic' condition) over the 2 h following nicotine or saline injection. *Significant decrease compared to ‘Veh+Veh+Nic' condition; n=5 for all conditions except MK886 (n=6). All data were presented as mean±SEM.