Figure 6.
Clofibrate blocked the effects of nicotine on firing of ventral tegmental area (VTA) dopamine cells. In single-cell electrophysiology experiments in anesthetized rats, nicotine significantly increased the firing rate of these cells, which were antidromically identified as projecting to the nucleus accumbens shell. This effect of nicotine was partially blocked by 200 mg/kg clofibrate and completely blocked by 300 mg/kg clofibrate. Administration of the PPAR-α antagonist MK886 (‘MK' 10 mg/kg, intraperitoneally) before clofibrate prevented clofibrate from altering the effects of nicotine. Histograms show firing of representative single cells over time in rats pretreated with (a) vehicle (‘Veh'), (b) 300 mg/kg clofibrate (‘Clof 300'), or (c) 10 mg/kg MK886 plus 300 mg/kg clofibrate (‘MK+Clof 300'). (d) Mean (±SEM) firing rates over time for the same three treatment conditions as panels a–c, and also after treatment with 200 mg/kg clofibrate. Arrows indicate time of nicotine (‘Nic') administration; n=9 for vehicle, n=7 for both doses of clofibrate, and n=5 for MK886+clofibrate.