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Risperidone ameliorates post-traumatic stress disorder-like symptoms in modified stress re-stress model.
- Source :
-
Neuropharmacology [Neuropharmacology] 2013 Dec; Vol. 75, pp. 62-77. Date of Electronic Publication: 2013 Jul 25. - Publication Year :
- 2013
-
Abstract
- The management for post-traumatic stress disorder (PTSD) involves chronic administration of drugs. We have modified the stress re-stress (SRS) model to study the effect of chronic administration of risperidone (RIS) after induction of PTSD in rats. On day-1 (D-1) rats underwent training session for elevated-plus maze (EPM) test. On D-2, rats were subjected to stress protocol of 2 h restraint and 20 min forced-swim test (FST) followed by halothane anesthesia. The rats were exposed to re-stress (FST) on D-8 and at six day intervals on D-14, D-20, D-26 and D-32. The rats were treated with RIS (0.01, 0.1 and 1.0 mg/kg; p.o.) and standard drug, paroxetine (PAX; 10.0 mg/kg; p.o.) from D-8 to D-32. RIS (0.1 mg/kg) and PAX ameliorated SRS-induced immobility. RIS in median dose reversed SRS-induced hypocorticosteronemia both in urine and plasma. RIS in median dose improved SRS-induced behavioral perturbations such as memory impairment and anxiety-like behavior in EPM and Y-maze tests. RIS (0.1 mg/kg) reversed SRS-induced increase in amygdalar serotonin level. RIS (0.1 mg/kg) increased the expression of hippocampal MR thereby reversing the SRS-induced decrease in MR/GR ratio. Pearson's analysis of data on D-32 showed that there was significant correlation of plasma corticosterone, amygdalar serotonin and hippocampal ratio of mineralocorticoid (MR)/glucocorticoid receptor (GR) with SRS-induced behavioral abnormalities. Hence, median dose of RIS shows anti-PTSD-like effect in the modified SRS model. PAX had earlier onset of action in ameliorating behavioral effects of PTSD compared to RIS. However, RIS showed anti-PTSD like effect in sub-therapeutic dose. The mode of anti-PTSD action of RIS seems to involve the HPA-axis and serotonergic system, whereas PAX did not show any significant action on these pathways. The effect of repeated treatment of drugs for PTSD can be evaluated using the modified SRS model.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antidepressive Agents, Second-Generation therapeutic use
Brain drug effects
Brain metabolism
Corticosterone metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Immobility Response, Tonic drug effects
Male
Maze Learning drug effects
Paroxetine therapeutic use
Rats
Swimming psychology
Time Factors
Antipsychotic Agents therapeutic use
Risperidone therapeutic use
Stress Disorders, Post-Traumatic drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 75
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 23891637
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2013.07.005