Fig. 5. Blocking allopregnanolone (AP) synthesis and signaling normalized the adverse impact of spatial confinement (SC) in CIN-depleted (CIN-d) mice.

The inhibitor of AP synthesis finasteride (FIN; 6 and 12 mg/kg, IP) dose-dependently countered SC-induced elevations in grooming duration (A) and PPI deficits in CIN-d mice (C), without affecting startle amplitude (B). Systemic administration of the AP antagonist isoAP (10 and 20 mg/kg, IP) also opposed the increase in grooming induced by SC (D). As expected, CIN-d led to the enhancement of startle amplitude (E), but isoAP did not affect this parameter. However, isoAP (10-20 mg/kg, IP, 10 min before testing) reversed PPI deficits in CIN-d mice (F). IsoAP infusion into the medial prefrontal cortex (mPFC) (1 μg/μl/mouse) also reversed the negative effects of SC on grooming (G). While no significant differences were found in startle amplitude (H), local isoAP infusions normalized PPI in CIN-d mice (I). All data were analyzed by two-way ANOVAs. ^P < 0.05; main effects for CIN-d. *P < 0.05; ***P < 0.001 for post-hoc comparisons between CIN-d and Ctrl mice treated with vehicle (represented by white bars). ^#P < 0.05; ^##P < 0.01; ^###P < 0.001 for comparisons between CIN-d mice injected with either the treatment or its vehicle. All data refer to SC‐exposed CIN-d and Ctrl male mice. Treatment doses are indicated under colored bars. All data are shown as means ± SEM. n = 6–8/group. For further details, see text and Supplementary Table 1E.