DAMGO, a μ-opioid receptor agonist, inhibits GABA release in yoked saline but not cocaine-extinguished rats. A, Recordings were performed on sagittal slices. Patched cells were located under the anterior commissure (AC) and the stimulating electrode was positioned 200–300 μm rostral to the recorded cell. Core, Core subcompartment of nucleus accumbens; IPAC, interstitial nucleus of the posterior part of the anterior commissure; Shell, shell subcompartment of nucleus accumbens. B, DAMGO dose-dependently inhibited evoked GABA IPSCs in yoked saline rats but not in rats that underwent cocaine self-administration and extinction [two-way ANOVA; F(1,80) = 8.94, p < 0.05 for the main effect of group (saline vs cocaine); F(3,80) = 3.92, p < 0.05 for interaction group × DAMGO]. Number of replicates is presented as number of cells/number of rats for each data point. Number of cells and rats is the same for D, E. C, Representative traces of eIPSCs with increasing doses of DAMGO (0, 10, 100, 1000 nm) in yoked saline and cocaine-extinguished rats. D, sIPSC amplitude was unchanged after treatment with DAMGO in yoked saline and cocaine-extinguished rats. E, sIPSC frequency was reduced by DAMGO in yoked saline but not cocaine-extinguished rats (two-way ANOVA; F(1,88) = 11.36, p < 0.05 for the main effect of group; F(3,88) = 3.78, p < 0.05 for the interaction group × DAMGO). F, Representative traces of sIPSCs in yoked saline (left) and cocaine-extinguished (right) rats with increasing DAMGO concentrations. Note the decrease in sIPSC frequency in yoked saline rats. G, mIPSC amplitude was unchanged by DAMGO in both yoked saline and cocaine-extinguished rats. H, mIPSC frequency was reduced by DAMGO in yoked saline but not cocaine-extinguished rats (two-way ANOVA; F(1,41) = 9.69, p < 0.05 for main effect of group; F(2,41) = 3.65, p < 0.05 for interaction group × DAMGO). Number of cells as in G. I, DAMGO hyperpolarized VP neurons in yoked saline rats but not in rats that underwent cocaine self-administration and extinction (two-way ANOVA; F(1,61) = 4.04, p < 0.05 for the main effect of group). J, DAMGO application dose-dependently decreased action potential (AP) frequency in yoked saline rats (44.12 ± 10.10% of baseline with 1000 nm DAMGO; one-way ANOVA; F(3,38) = 6.44, p < 0.05). Number of cells is presented above the number of rats (in parentheses). *p < 0.05 comparing the two groups in a given DAMGO concentration using two-way ANOVA and Bonferroni post hoc analysis. #p < 0.05 compared with baseline using one-way ANOVA and Bonferroni post hoc analysis. Data presented as mean ± SEM.