Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress

Cogent evidence has shown that schizophrenia vulnerability is enhanced by psychosocial stress in adolescence, yet the underpinnings of this phenomenon remain elusive. One of the animal models that best capture the relationship between juvenile stress and schizophrenia is isolation rearing (IR). This manipulation, which consists in subjecting rats to social isolation from weaning through adulthood,

These results show that 5αR inhibition counters the PPI deficits induced by IR, possibly through limbic changes in pregnenolone and/or allopregnanolone concentrations.

We studied the impact of the prototypical 5αR inhibitor finasteride (FIN) on the PPI deficits and NAcc steroid profile of IR-subjected male rats, in comparison with socially reared (SR) controls.

FIN (25-100 mg/kg, i.p.) dose-dependently countered IR-induced PPI reduction, without affecting gating integrity in SR rats. The NAcc and striatum of IR-subjected rats displayed several changes in neuroactive steroid profile, including a reduction in pregnenolone in both SR and IR-subjected groups, as well as a decrease in allopregnanolone content in the latter group; both effects were significantly opposed by FIN. Conclusions: These results show that 5αR inhibition counters the PPI deficits induced by IR, possibly through limbic changes in pregnenolone and/or allopregnanolone concentrations.