Allopregnanolone Mediates the Exacerbation of Tourette-Like Responses by Acute Stress in Mouse Models

The study investigated the role of neurosteroids in stress-induced exacerbation of Tourette syndrome (TS) symptoms using the D1CT-7 mouse model. Spatial confinement, a moderate stressor, increased levels of progesterone and its derivatives, particularly allopregnanolone, in the prefrontal cortex. Allopregnanolone, administered at 5-15 mg/kg, exacerbated TS-like symptoms in D1CT-7 mice but not in wild-type mice, and these effects were mitigated by haloperidol. Additionally, finasteride, an inhibitor of allopregnanolone synthesis, suppressed the stress-induced symptoms. The findings suggested that stress exacerbates TS symptoms through increased allopregnanolone synthesis, highlighting finasteride as a potential therapeutic option.