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Involvement of allopregnanolone in the anti-PTSD-like effects of AC-5216
- Source :
- Journal of Psychopharmacology. 30:474-481
- Publication Year :
- 2016
- Publisher :
- SAGE Publications, 2016.
-
Abstract
- Cholesterol import into mitochondria through the translocator protein (18 KDa) (TSPO) is the starting point and an important rate-limiting step in neurosteroidogenesis. For this reason TSPO has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD). In an effort to explore the role of TSPO in mediating the anti-PTSD effect, we first assessed the effects of the TSPO ligand AC-5216 in alleviating the enhanced anxiety and fear response in a time-dependent sensitization (TDS) procedure, a rat PTSD animal model. In the present study, we showed that chronic treatment with AC-5216 caused significant suppression of the enhanced anxiety and contextual fear induced in post-TDS rats; these effects were blocked by PK11195. Furthermore, AC-5216 treatment increased the levels of allopregnanolone in the serum, prefrontal cortex, and hippocampus of post-TDS rats, and these effects were antagonized by PK11195. These results demonstrate that AC-5216 has a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Prefrontal Cortex
Hippocampus
Pregnanolone
Anxiety
Motor Activity
Rats, Sprague-Dawley
Stress Disorders, Post-Traumatic
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Translocator protein
Animals
Pharmacology (medical)
Prefrontal cortex
Sensitization
Post-traumatic stress disorder (PTSD)
Pharmacology
biology
Allopregnanolone
Fear
Isoquinolines
medicine.disease
Rats
Disease Models, Animal
Psychiatry and Mental health
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Anti-Anxiety Agents
Cholesterol import
chemistry
Purines
biology.protein
medicine.symptom
Psychology
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14617285 and 02698811
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Journal of Psychopharmacology
- Accession number :
- edsair.doi.dedup.....560d372e15327f3448f2932dd349d2d3