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The Neurosteroidogenic Enzyme 5α-Reductase Mediates Psychotic-Like Complications of Sleep Deprivation
- Source :
- Neuropsychopharmacology. 42:2196-2205
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone. SD selectively enhanced 5αR expression and activity, as well as AP levels, in the prefrontal cortex; furthermore, finasteride (10–100 mg/kg, IP) dose-dependently ameliorated PPI deficits, hyperactivity, and risk-taking behaviors, in a fashion akin to the antipsychotic haloperidol and the mood stabilizer lithium carbonate. Finally, PPI deficits were exacerbated by allopregnanolone (10 mg/kg, IP) and attenuated by progesterone (30 mg/kg, IP) in SD-subjected, but not control rats. Collectively, these results provide the first-ever evidence that 5αR mediates a number of psychosis- and mania-like complications of SD through imbalances in cortical levels of neuroactive steroids.
- Subjects :
- Male
Cholestenone 5 alpha-Reductase
Reflex, Startle
Psychosis
medicine.medical_specialty
Neuroactive steroid
medicine.drug_class
medicine.medical_treatment
Poison control
Pregnanolone
Gene Expression Regulation, Enzymologic
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
5-alpha Reductase Inhibitors
0302 clinical medicine
Internal medicine
Haloperidol
medicine
Animals
Antipsychotic
Pharmacology
Psychiatry and Mental Health
Dose-Response Relationship, Drug
business.industry
Finasteride
Allopregnanolone
Brain
Mood stabilizer
medicine.disease
Rats
030227 psychiatry
Disease Models, Animal
Psychiatry and Mental health
Sleep deprivation
Endocrinology
Acoustic Stimulation
Psychotic Disorders
chemistry
Sleep Deprivation
Steroids
Original Article
medicine.symptom
business
030217 neurology & neurosurgery
Antipsychotic Agents
medicine.drug
Clinical psychology
Subjects
Details
- ISSN :
- 1740634X and 0893133X
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....a68521c6850b8c5cddbfb178ee6031be