A neuroactive steroid, pregnenolone, alters the striatal dopaminergic tone before and after puberty

Neuroactive steroids are known to modulate excitability in neurons. Neuronal activity during early development is critical to normal development of the brain. A neuroactive steroid, pregnenolone, was administered (10 microg/g) to rats from postnatal day 3 (PD 3) through PD 7. Dopamine (DA), serotonin (5-HT) and their metabolites were measured in the striatum. The results showed that neonatal treatment with pregnenolone increases DA and 5-HT turnover in the striatum at 3 weeks of age. The increased 5-HT turnover in the pregnenolone-treated animals was normalized at 14 weeks of age whereas the DA turnover in the pregnenolone-treated group was lower than in the control group. The present study indicated that pregnenolone treatment during the neonatal period induced abnormal development of the striatal dopaminergic function in adulthood.