Fig. 4: DA over-transmission in the mPFC during adolescence mediates schizophrenia-like social deficits.

a Schematic of the co-injection of TH-Cre and DIO-ChR2-mCherry viruses into the VTA of juvenile C57 mice (3 weeks). b Upper, representative AP traces showing optogenetic activation of DA neurons in VTA slices (mCherry-positive) by 473-nm light stimulation (L-stim). Lower, representative amperometric traces showing the L-stim induced DA release in the NAc and mPFC slices. Data from 3 mice. c Schematic and statistics of sniffing time/frequency in the home-cage social test of the ChR2-expressing mice vs control mice following L-stim trains in the mPFC. d Schematic of bilateral cannula application of the D2R agonist quinpirole (Qp) into the mPFC and the experimental procedure. e Representative AP traces and statistics showing the inhibitory effect of Qp (50 nM) on the excitability of D2R-positive cortical neurons in the mPFC (Data from 3 mice and presented as mean ± SEM). f–h Representative heat maps and statistics of the three-chamber social interaction test of juvenile (6–8 weeks) mice following the local application of Qp vs saline in the mPFC. i–k Representative heat maps and statistics of the social novelty test of the Qp- vs saline-treated juvenile mice as described in f–h. l Statistics of investigation frequency and investigation time in the home cage social test of the Qp- vs saline-treated juvenile mice. m Schematic of bilateral cannula application of Qp into the NAc and the experimental procedure. n Representative AP traces and statistics showing the inhibitory effect of Qp (50 nM) on the excitability of D2R-positive cortical neurons in the NAc (Data from 3 mice and presented as mean ± SEM). o–q Representative heat maps and statistics of the three-chamber social interaction test of juvenile (6–8 weeks) mice following the local application of Qp vs saline in the NAc. r–t Representative heat maps and statistics of the three-chamber social novelty test of juvenile mice following the local application of Qp vs saline in the NAc. u Investigation frequency and investigation time in the home cage social test of juvenile mice following the local application of Qp vs saline in the NAc. Data are shown as box-and-whisker plots, with the median represented by the central line inside each box, the 25th and 75th percentiles represented by the edges of the box, and the whiskers extending to the most extreme data points. Ordinary two-way ANOVA followed by Bonferroni’s post-hoc test for (g, j, p, s), paired two-tailed Student’s t-test for (e, n), or two-tailed Mann-Whitney test for (c, h, k, l, q, t, u), *P < 0.05, **P < 0.01, ***P < 0.001, n.s. no significant difference. Source data are provided as a Source Data file.