a Timeline showing juvenile social isolation (jSI), Cre-dependent excitatory DREADD (eDREADD) viral injection (p42) in PV-Cre mice, and sociability and anxiety behavior testing (adult, p60–80). b Immunohistochemistry validation of co-localization between mCherry (eDREADD, red) and parvalbumin (PV) antibody (blue). Scale bar left = 100 μm. Scale bar right = 50 μm. c Full behavioral results from the 3-chamber test for sociability show that jSI mice treated with SAL do not show a social preference; however, mice treated with CNO show a significant social preference. GH mice show a significant social preference under both SAL and CNO conditions (two-way repeated measures ANOVA, GH: drug x stimulus interaction F(1,7) = 0.13, p = 0.73 jSI: drug x stimulus interaction, F(1,11) = 6.28, *p = 0.03 followed by post hoc Bonferroni corrected t tests, *p < 0.05, **p < 0.01, ***p < 0.001). n = 12 mice jSI, 8 mice GH. d Juvenile socially isolated JSI adult mice show a significant increase in social interaction in the first 2 min of behavior testing when treated with CNO compared with SAL (paired t test, t = 2.75, df = 11, *p = 0.02). e Neither jSI nor dmPFC-PVI activation with CNO has significant effects on anxiety behavior in the open field (mixed effects ANOVA, OF: effect of housing, p = 0.73, F(1,16) = 0.12, effect of the drug, F(1,16) = 0.12, p = 0.74, interaction, F(1,16) = 1,26, p = 0.28), elevated-plus maze (EPM: effect of housing, F(1,19) = 0.68, p = 0.42, effect of the drug, F(1,19) = 0.06, p = 0.81, interaction, F(1,16) = 0.04, p = 0.85), or the light–dark box (LD, effect of housing, F(1,16) = 0.09, p = 0.77, effect of the drug, F(1,16) = 1.03, df = 1, p = 0.32, interaction F(1,16) = 3.36, p = 0.09). All error bars reflect + /− SEM. See related Supplementary Figs. 16 and 17. Source data are available as a Source Data file.