Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens

Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada

Research output: Contribution to journalArticle

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 (100 mg/kg, IP) and subchronic (7 days; 100 mg/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.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalPsychoneuroendocrinology
Volume74
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

Finasteride
Nucleus Accumbens
Proteomics
Oxidoreductases
Tourette Syndrome
Alopecia
Dopamine Receptors
Prostatic Hyperplasia
Therapeutic Uses
Therapeutics
Pharmaceutical Preparations
Progesterone
Electrophoresis
Testosterone
Dopamine
Mass Spectrometry
Schizophrenia
Steroids
Psychology
Enzymes

Keywords

  • Finasteride
  • Gene ontology
  • Proteomics
  • Rat brain

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Exploring the neural mechanisms of finasteride : a proteomic analysis in the nucleus accumbens. / Soggiu, Alessio; Piras, Cristian; Greco, Viviana; Devoto, Paola; Urbani, Andrea; Calzetta, Luigino; Bortolato, Marco; Roncada, Paola.

In: Psychoneuroendocrinology, Vol. 74, 01.12.2016, p. 387-396.

Research output: Contribution to journalArticle

Soggiu, Alessio ; Piras, Cristian ; Greco, Viviana ; Devoto, Paola ; Urbani, Andrea ; Calzetta, Luigino ; Bortolato, Marco ; Roncada, Paola. / Exploring the neural mechanisms of finasteride : a proteomic analysis in the nucleus accumbens. In: Psychoneuroendocrinology. 2016 ; Vol. 74. pp. 387-396.
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