Fig. 4: DREADD-driven attenuation of hyperdopaminergic states ameliorates social interaction deficits of epidermal growth factor model rats.

a AAV vectors carrying the hM4Di gene plus mCherry (hM4Di) or mCherry alone (mCherry) were microinjected into the VTA of EGF model rats or control rats. The hM4Di ligand clozapine N-oxide (CNO) was subchronically administered to these rats with the aid of an osmotic pump. The DREADD effects on firing rates of ventral tegmental area (VTA) dopaminergic neurons were ascertained in EGF model rats carrying the hM4Di gene by comparison with those in EGF model rats or control rats expressing mCherry alone. (n = 55 cells, 6 rats for control + mCherry; n = 52 cells, 7 rats for EGF + mCherry, n = 53 cells, 7 rats for EGF + hM4Di), by Kruskal–Wallis followed by Steel post hoc test. b The sniffing duration of these animals were measured as their social interaction scores (n = 10 for control rats + mCherry, n = 10 for EGF rats + mCherry, n = 10 for EGF + hM4Di), by Kruskal–Wallis followed by Steel post hoc test. c Dopamine release from VTA dopaminergic neurons was monitored in the prelimbic cortex. The baseline levels and social interaction-triggered release of dopamine from the prelimbic cortex were compared among these three groups of rats (n = 6 for control + mCherry, n = 7 for EGF model rats + mCherry, n = 6 for EGF model rats + hM4Di) across 20 bins (1 min each) by two-way repeated ANOVA followed by Tukey post hoc test with the Holm’s compensation. *P < 0.05, **P < 0.01, ***P < 0.001.