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. 2023 May 17;48(9):1288–1299. doi: 10.1038/s41386-023-01603-6

Fig. 4. Allopregnanolone (AP) increased Tourette syndrome- (TS) relevant responses in CIN-depleted (CIN-d) but not control (Ctrl) male mice.

Fig. 4

Spatial confinement (SC; 40 min) increased the levels of A pregnenolone (PREG); B progesterone (PROG); C 5α-dihydroprogesterone (DHP); and D AP in the prefrontal cortex (PFC) of CIN-d and Ctrl male mice. While systemic AP injections (6-12 mg/kg, IP, 5 min before testing) did not alter E grooming duration in Ctrl mice, it increased this response F in CIN-d mice after 20 min from its administration. AP elicited no significant effect on G startle amplitude in either Ctrl or CIN-d mice but did exacerbate H PPI deficits in CIN-d mice. Similarly, AP administration into the medial prefrontal cortex (mPFC) (1 µg/µl/mouse) failed to increase grooming duration in I Ctrl mice but markedly enhanced this response J in CIN-d mice. AP failed to modify startle response K but exacerbated PPI impairments L. Administration of AP into the dorsolateral striatum (DLS) increased moderately total grooming duration in N CIN-d, but not control (M) mice. While CIN-d mice showed increased acoustic startle amplitude (O) and reduced PPI (P), these effects were not modified by AP. OP < 0.05; OOP < 0.01; OOOP < 0.001 for post-hoc comparisons between the effects of AP and vehicle at the same time from administration. ^P < 0.05; ^^^P < 0.001 for main effect of CIN-d. *P < 0.05; ***P < 0.001 for post-hoc comparisons between vehicle (represented by white bars)-treated CIN-d and Ctrl mice. ##P < 0.01; ###P < 0.001 for comparisons between CIN-d mice injected with AP and its vehicle; +++P < 0.001 for post-hoc comparisons between Ctrl and CIN-d mice treated with AP. Grooming data were analyzed by two-way, repeated-measure ANOVA designs. Acoustic startle and PPI data were analyzed with two-way ANOVAs. All data refer to freely moving CIN-d and Ctrl male mice. AP doses are reported under colored bars. All data are shown as means ± SEM. n = 6-8/group. For further details, see text and Supplementary Table 1D.