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Cited by 156Neuroscience and Neuropharmacology ResearchTreatment of Major DepressionStress Responses and Cortisol

SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake

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Pinna, Graziano, Costa, Erminio, Guidotti, Alessandro·2009·Current Opinion in Pharmacology
DOI 10.1016/j.coph.2008.12.006PMC PMC2670606
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Abstract

Brain principal glutamatergic neurons synthesize 3alpha-hydroxy-5alpha-pregnan-20-one (Allo), a neurosteroid that potently, positively, and allosterically modulates GABA action at GABA(A) receptors. Cerebrospinal fluid (CSF) Allo levels are decreased in patients with posttraumatic stress disorder (PTSD) and major depression. This decrease is corrected by fluoxetine in doses that improve depressive symptoms. Emotional-like behavioral dysfunctions (aggression, fear, and anxiety) associated with a decrease of cortico-limbic Allo content can be induced in mice by social isolation. In socially isolated mice, fluoxetine and analogs stereospecifically normalize the decrease of Allo biosynthesis and improve behavioral dysfunctions by a mechanism independent from 5-HT reuptake inhibition. Thus, fluoxetine and related congeners facilitate GABA(A) receptor neurotransmission and effectively ameliorate emotional and anxiety disorders and depression by acting as selective brain steroidogenic stimulants (SBSSs).

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Authors
Pinna, G., Costa, E., & Guidotti, A.
Affiliations
University of Illinois Chicago (US)
Corresponding author
Pinna, Graziano
ORCID
Venue
Current Opinion in Pharmacology
Publisher
Elsevier BV
Published
2009-02
Volume
9
Issue
1
Pages
24-30
ISSN
1471-4892 (ISSN-L)
DOI
10.1016/j.coph.2008.12.006
PMC
PMC2670606
OpenAlex
W2002863546
Cited by
156
References
3
Citations by year
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FWCI
0.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH056890)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
selective serotonin reuptake inhibitors, fluoxetine, 3alpha-hydroxy-5alpha-pregnan-20-one, neurosteroids, GABA-A receptor modulation, social isolation, post-traumatic stress disorder, major depressive disorder, anxiety disorders
MeSH terms
Animals, Mental Disorders, Brain, Fluoxetine, gamma-Aminobutyric Acid, Humans, Synaptic Transmission, Pregnanolone, Receptors, GABA-A, Social Isolation, Selective Serotonin Reuptake Inhibitors, Mood Disorders

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