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Expanding the therapeutic potential of neuro(active)steroids : a promising strategy for hyperdopaminergic behavioral phenotypes

Scheggi, Simona ; Concas, Luca ; Corsi, Sara LU ; Carta, Manolo ; Melis, Miriam and Frau, Roberto (2024) In Neuroscience and Biobehavioral Reviews 164.
Abstract

Imbalances in dopamine activity significantly contribute to the pathophysiology of several neuropsychiatric disorders, including addiction, ADHD, schizophrenia, impulse control disorders, and Parkinson's Disease. Neuro(active)steroids, comprising endogenous steroids that finely modulate neuronal activity, are considered crucial regulators of brain function and behavior, with implications in various physiological processes and pathological conditions. Specifically, subclasses of Neuro(active)steroids belonging to the 5α reductase pathway are prominently involved in brain disorders characterized by dopaminergic signaling imbalances. This review highlights the neuromodulatory effects of Neuro(active)steroids on the dopamine system and... (More)

Imbalances in dopamine activity significantly contribute to the pathophysiology of several neuropsychiatric disorders, including addiction, ADHD, schizophrenia, impulse control disorders, and Parkinson's Disease. Neuro(active)steroids, comprising endogenous steroids that finely modulate neuronal activity, are considered crucial regulators of brain function and behavior, with implications in various physiological processes and pathological conditions. Specifically, subclasses of Neuro(active)steroids belonging to the 5α reductase pathway are prominently involved in brain disorders characterized by dopaminergic signaling imbalances. This review highlights the neuromodulatory effects of Neuro(active)steroids on the dopamine system and related aberrant behavioral phenotypes. We critically appraise the role of pregnenolone, progesterone, and allopregnanolone on dopamine signaling. Additionally, we discuss the impact of pharmacological interventions targeting 5α reductase activity in neuropsychiatric conditions characterized by excessive activation of the dopaminergic system, ranging from psychotic (endo)phenotypes and motor complications to decision-making problems and addiction.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Allopregnanolone, Dopamine, Neuroactive steroids, Neurosteroids, Pregnenolone, Sensorimotor gating
in
Neuroscience and Biobehavioral Reviews
volume
164
article number
105842
publisher
Elsevier
external identifiers
  • pmid:39103066
  • scopus:85200770794
ISSN
0149-7634
DOI
10.1016/j.neubiorev.2024.105842
language
English
LU publication?
yes
id
81ab74ff-f71e-4d5c-b264-a1455638c1a4
date added to LUP
2024-09-06 13:23:01
date last changed
2024-09-06 13:23:31
@article{81ab74ff-f71e-4d5c-b264-a1455638c1a4,
  abstract     = {{<p>Imbalances in dopamine activity significantly contribute to the pathophysiology of several neuropsychiatric disorders, including addiction, ADHD, schizophrenia, impulse control disorders, and Parkinson's Disease. Neuro(active)steroids, comprising endogenous steroids that finely modulate neuronal activity, are considered crucial regulators of brain function and behavior, with implications in various physiological processes and pathological conditions. Specifically, subclasses of Neuro(active)steroids belonging to the 5α reductase pathway are prominently involved in brain disorders characterized by dopaminergic signaling imbalances. This review highlights the neuromodulatory effects of Neuro(active)steroids on the dopamine system and related aberrant behavioral phenotypes. We critically appraise the role of pregnenolone, progesterone, and allopregnanolone on dopamine signaling. Additionally, we discuss the impact of pharmacological interventions targeting 5α reductase activity in neuropsychiatric conditions characterized by excessive activation of the dopaminergic system, ranging from psychotic (endo)phenotypes and motor complications to decision-making problems and addiction.</p>}},
  author       = {{Scheggi, Simona and Concas, Luca and Corsi, Sara and Carta, Manolo and Melis, Miriam and Frau, Roberto}},
  issn         = {{0149-7634}},
  keywords     = {{Allopregnanolone; Dopamine; Neuroactive steroids; Neurosteroids; Pregnenolone; Sensorimotor gating}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience and Biobehavioral Reviews}},
  title        = {{Expanding the therapeutic potential of neuro(active)steroids : a promising strategy for hyperdopaminergic behavioral phenotypes}},
  url          = {{http://dx.doi.org/10.1016/j.neubiorev.2024.105842}},
  doi          = {{10.1016/j.neubiorev.2024.105842}},
  volume       = {{164}},
  year         = {{2024}},
}