Ruolo dei neurosteroidi nella modulazione dopaminergica

Cogent evidence shows that neurosteroids play a key role in the modulation of dopaminergic responses in the brain. Several findings have shown that these compounds can affect the severity of DRT- induced effects in well validated animal models. Over the last few years, we have characterized that inhibition of 5 alpha- reductase (5AR), the key enzyme for androgen metabolism and neurosteroid synthesis, elicts antidopaminergic effects. The 5AR inhibitor, finasteride (FIN), is currently approved for the therapy of benign prostatic hyperplasia and androgenic alopecia. We found that, in rodents, FIN attenuates the severity of behavioral manifestations induced by dopaminergic agents, including deficits of sensorimotor gating as well as repetitive and compulsive responses. Unlike other antidopaminergic agents, however, FIN does not elicit catalepsy or other extrapyramidal side-effects. To extend these findings, this thesis is aimed at the assessment of the role of other key neurosteroidogenic enzymes in PPI, such as 17α-hydroxylase/C17,20 lyase (CYP17A1), 3α- and 3β-hydroxysteroid dehydrogenase (HSD), in Sprague-Dawley rats and we tested the drug like FIN in a reserpinized rat probability discounting task, a behavioral paradigm aimed at capturing critical behavioral aspect of gambling disorder, namely the preference for large, uncertain rewards, rather than small certain rewards.