Repeated cocaine treatment reduced NAc Na⁺ currents and caused a depolarizing shift in the voltage dependence of activation. A, NAc neurons (n = 33) from cocaine-pretreated rats exhibited significantly (t₆₈ = 2.75;p = 0.0075) reduced peak whole-cell Na⁺ currents (measured at −20 mV) as compared with neurons (n = 37) obtained from saline-pretreated rats. Results are presented as current density to normalize for capacitance (see Results). B, Recordings showingI–V relationship for Na⁺ currents in a control and a cocaine-pretreated NAc neuron. C, Plots of the I–V curves for the two neurons shown inB. D, Cocaine pretreatment caused a depolarizing shift in the voltage dependence of activation and reduced the slope factor (k). Values were obtained for each neuron at each membrane voltage, and the mean ± SEM were plotted. Half-maximal activation (V_1/2) and slope (k) values were obtained individually for each neuron and compared with t tests. Half-maximal activation occurred at significantly (t₂₈ = 2.26; p = 0.031) more depolarized potentials in cocaine-pretreated neurons (−40.3 ± 1.8 mV;n = 16) as compared with saline-pretreated neurons (46.1 ± 1.2; n = 14). The slope factor was also significantly decreased (t₂₈ = 3.13;p = 0.004) in the cocaine group (8.85 ± 0.8) as compared with the saline group (4.01 ± 0.8). Note that theV_½ and k values shown in the figure were derived from the curves fitted to the mean values depicted in the figure, not from the mean values (given here) obtained by averaging all of the neurons in the sample.E, The voltage dependence of inactivation was not altered by repeated cocaine treatment. Values were obtained from the mean ± SEM as in B (n = 16 for cocaine; n = 13 for saline). Note that repeated administration of lidocaine failed to produce effects similar to those of cocaine: Na⁺ current density = 0.81 ± 0.058, n = 9; activationV_½ = −42.4 ± 1.8,k = 5.2 ± 0.8, n = 8; and inactivation V_½ = −60.6 ± 2.5, k = 7.0 ± 0.4, n = 9. None of these values was significantly different from control (t tests). See Figure 5 legend for details regarding activation and inactivation curves.