Figure 3.

Effects of cocaine exposure on GABAergic inhibition of VTA neurons. a, Repeated cocaine treatment reduced the amplitude of maximal IPSCs in dopamine neurons. Top, Sample IPSCs in response to stimuli of incremental intensities (20 to 140 μA). Scales: 100 pA, 15 ms. Bottom, the mean amplitude of maximal IPSCs after 1-7 d saline or cocaine treatment, and 12 d withdrawal from 7 d cocaine treatment (19 d, n = 17-25 for each bar). b, Mean maximal IPSC amplitudes in non-dopamine neurons (n = 15-19). Scales: 150 pA, 15 ms. c, Samples (top) and average amplitudes (below) of currents induced by puffing muscimol (20 μM, arrow) at the soma of dopamine neurons. (* p < 0.01, t-test). Scales: 500 pA, 3s. d, Repeated cocaine treatment (5-7 d) had no effect on the mean mIPSC frequency but decreased the mean mIPSC amplitude (*p < 0.01, t-test) and significantly shifted the mIPSC amplitude distribution (bin size 2 pA) towards smaller values (p < 0.001, Kolmogorov-Smirnov test). Sample traces of mIPSCs are shown at the top. Scales: 80 pA, 250 ms. e, Effect of repeated cocaine exposure on the probability for spike initiation in dopamine neurons. Top, Examples of APs induced by 80 μA stimulation for 5 d saline-treated rat before (left) and after (right) BMI (20 μM). Scales: 30 pA, 10 ms. Bottom, Input-output curves (fit with the Boltzmann function) of probability of APs induced by graded stimuli for 5-7 d saline- and cocaine-treated rats. Error bars, s.e.m (n = 8-10).