C48/80 reduces intrinsic excitability of Drd1-MSNs in the NAc core. A, Intradermal injection of C48/80 induces scratching bouts in mice (n = 13–14 mice/group, ***p < 0.0001, U = 0, Mann–Whitney U test). B, The EPMT shows that C48/80 treatment reduces the time spent in open arms compared with saline injection (n = 13–14 mice/group, **p = 0.0069, U = 36.50, Mann–Whitney U test). C, C48/80 reduces the open arms entries on the EPM (***p < 0.0001, t(25) = 4.94, Student’s t test). D, The OFT shows that C48/80 treatment reduces the time spent in central zone compared with saline injection (n = 13–14 mice/group, ***p = 0.0003; U = 20, Mann–Whitney U test). E, C48/80 treatment reduces the travel distance on the OFT (***p < 0.0001, U = 15, Mann–Whitney U test). F, Representative images show the identification of Drd1-MSNs (left) and Drd2-MSNs (right) in coronal NAc slices from Drd1-tdTomato and Drd2-eGFP mice, respectively. G, Schematic representation of the experimental schedule and recording site. H, A fluorescent-positive neuron was recorded by patch clamp pipette in fluorescent and DIC image modes. I, Bar graph and scatter plot for rest membrane potential (RMP) in Drd1-MSNs in slices from the saline-treated and C48/80-treated mice (n = 32–39 neurons/group, *p = 0.04 U = 446.5, Mann–Whitney U test). J, Same as I for rheobase (n = 32–39 neurons/group, *p = 0.0105, t(69) = 2.631, Student’s t test). K, Sample traces of action potentials (APs) obtained in Drd1-MSNs in slices from saline-treated and C48/80-treated mice. L, The number of evoked action potentials in response to the increasing depolarizing current steps in Drd1-MSNs from saline-treated and C48/80-treated mice (F(interaction 8,536) = 2.384, p = 0.0157; F(treatments 1,67) = 7.241, **p = 0.0090, two-way ANOVA with repeated measure). M, Bar graph and scatter plot for RMP in Drd2-MSNs in slices from the saline-treated (black) and C48/80-treated (green) mice (n = 25–26 neurons/group, p = 0.6261, t(49) = 0.4903, Student’s t test). N, Same as M for rheobase (n = 25–26 neurons/group, p = 0.2363, U = 263, Mann–Whitney U test). O, Sample traces of APs obtained in Drd2-MSNs in slices from saline-treated and C48/80-treated mice. P, The number of evoked action potentials in response to the increasing depolarizing current steps in Drd2-MSNs from saline-treated and C48/80-treated mice (F(interaction 8,384) = 0.3561, p = 0.9428; F(treatments 1,48) = 4575, p = 0.5020, two-way ANOVA with repeated measure).