The Neurosteroidogenic Enzyme 5α-Reductase Mediates Psychotic-Like Complications of Sleep Deprivation

The study investigated the role of the enzyme 5α-reductase (5αR) in the psychotic-like complications of acute sleep deprivation (SD) in rats. It was found that SD increased 5αR expression and activity, as well as levels of the neurosteroid allopregnanolone (AP) in the prefrontal cortex. Administration of the 5αR inhibitor finasteride reduced SD-induced behavioral and neuroendocrine alterations, such as PPI deficits, hyperactivity, and risk-taking behaviors, similar to the effects of antipsychotic and mood stabilizer drugs. Additionally, allopregnanolone exacerbated, while progesterone attenuated, PPI deficits in SD-subjected rats. These findings suggested that 5αR plays a significant role in mediating the psychosis- and mania-like effects of SD through neuroactive steroid imbalances in the cortex.