Fig. 6: Pathogenic effects of the D2R antagonist haloperidol on social deficits.

a Illustration showing the facilitatory effect of the D2R antagonist haloperidol (Halo) on DA transmission by targeting presynaptic D2Rs. b Schematic and representative traces showing increased DA release (evoked by a burst of electric stimulation [Estim, 50 pulses at 80 Hz] at the medial forebrain bundle) in the mPFC in vivo following i.p. application of Halo (0.4 mg/kg) in juvenile C57 mice. Data from 3 mice. c Representative trace and statistics of spontaneous APs of cortical neurons in mPFC slices in response to DA application (Data are presented as mean ± SEM). Data from 4 mice. d Left, illustration showing the dual effects of Halo on DA transmission by targeting presynaptic and postsynaptic D2Rs. Middle and right, representative traces and statistics of spontaneous APs of mPFC cortical neurons in response to Halo application. Data from 3 mice. e Schematic of bilateral cannula application of Halo into the VTA and the experimental procedure. f-h Representative heat maps and statistics of three-chamber social interaction time in juvenile (6–8 weeks) C57 mice following local application of Halo vs saline control in the VTA. i-k Representative heat maps and statistics of the social novelty test in Halo- vs saline-treated juvenile C57 mice. l Statistics of investigation time in juvenile C57 mice following local application of Halo vs saline control in the VTA in the home-cage social test. 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), two-tailed paired Student’s t-test for (c), or two-tailed Mann-Whitney test for (h, k, l), *P < 0.05, **P < 0.01, ***P < 0.001, n.s. no significant difference. Source data are provided as a Source Data file.