Voluntary nicotine consumption elevates VTA DA neuronal activity. A, Nicotine self-administration in the NIC group during a 2 month training under fixed-ratio schedules of reinforcement (FR1, FR2, and FR5). When responding was stable, the nicotine unit dose was increased from 30 to 60 μg/kg/infusion (arrow). Data are shown as mean ± SEM responses on the active (red circles) and inactive (white circles) nose-pokes. B, Oscilloscope traces of impulses from three VTA DA neurons showing typical recordings of two regular and one fast-firing VTA DA neuron in SAL, YOKED, and NIC rats, respectively. C, Analysis of firing activity of VTA DA neurons in SAL, YOKED, and NIC rats. Bar charts show firing rates as a function of the treatment that each group received. D, Histograms showing the distribution of VTA DA firing rates in SAL and NIC rats. Scale on the y-axis of the histograms corresponds only to the histogram bars. Solid lines on each of the graphs represent best-fit normal distribution curves for the histogram data. E, Analysis of the bursting activity of VTA DA neurons in SAL, YOKED and NIC rats. Bar charts show percentage of spikes in bursts as a function of the treatment that each group received. F, The frequency (left axis) or burst firing (right axis) was independent of the amount of nicotine self-administered. The dot chart represents the average firing rate (closed circles) and the average bursting activity (open circles) for all the VTA DA neurons recorded in each rat as a function of the total amount of self-administered nicotine. There is no correlation between bursting or firing activity and the total amount of nicotine self-administered by the NIC rats. Pearson correlation calculation; firing rates: Pearson r = 0.20, R² = 0.04; bursting activity: Pearson r = 0.16, R² = 0.03. A one-sample Kolmogorov–Smirnov test was used to test normal distribution. ***p < 0.001 versus VTA DA activity in SAL rats. Numbers refer to numbers of VTA DA neurons recorded.