title: Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens.
abstract: The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia. In rat models of these conditions, FIN has been shown to block the effects of dopamine receptors in the nucleus accumbens (NAcc), a key terminal of the dopamine mesolimbic system. The biological underpinnings of these effects, however, remain mostly elusive. To elucidate the neurochemical networks that may be responsible for the behavioral effects of FIN, we evaluated the proteomic profile of the NAcc following acute (100mg/kg, IP) and subchronic (7 days; 100mg/kg/day, IP) treatment with this drug, in comparison with vehicle treatment (n=5/group). Two-dimensional electrophoresis (2-DE) analysis coupled to mass spectrometry revealed significant changes in the expression of nine proteins (CRMP2, PSMD1, STX18, KCNC3, CYP255, GABRP, GABT, PRPS1, CYP2B3), which were further analyzed by ontological classification (PANTHER). These results point to a number of novel potential chemical targets of FIN, and may help elucidate the underpinnings of FIN's behavioral effects and therapeutic potential for neuropsychiatric disorders.
authors.affiliation: Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Soggiu
authors.affiliation: Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Piras
authors.affiliation: Fondazione S.Lucia-IRCSS, Roma, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Greco
authors.affiliation: Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, CA, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Devoto
authors.affiliation: Fondazione S.Lucia-IRCSS, Roma, Italy; Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Chair of Respiratory Medicine, Rome, Italy.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, University of Utah, Salt Lake City, UT, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.affiliation: Istituto Sperimentale Italiano "Lazzaro Spallanzani", Milano, Italy. Electronic address: paola.roncada@istitutospallanzani.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Roncada
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018120:Finasteride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D020543:Proteome / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058891:5-alpha Reductase Inhibitors; D020543:Proteome; D018120:Finasteride
keywords: Finasteride; Gene ontology; Proteomics; Rat brain