Repeated olanzapine treatment mitigates PTSD like symptoms in rats with changes in cell signaling factors.
Post Traumatic Stress Disorder is an anxiety disorder with prolonged distortion of rational behavior. In this study, we report the preclinical potential of olanzapine (OLZ) in the treatment of PTSD. Since the atypical antipsychotics have modulating effects on cell protective and destructive factors, we tested the effects of OLZ in PTSD regarding these cell modulating factors. Rats, when subjected to stress-restress (SRS) model of PTSD, showed a derangement in cell protective factors like the decline in BDNF, ERK, and CREB. While the adversarial factors like caspase-3 were enhanced. Four weeks treatment with OLZ at doses of 1 and 10 mg/kg significantly mitigated the SRS-induced derangement related to PTSD. OLZ at doses of 1 and 10 mg/kg enhanced BDNF, ERK and CREB levels which were reduced by SRS in PTSD animals. Further, at the fore mentioned doses it also inhibited the elevation of caspase-3 a downstream apoptotic factor. Besides, OLZ also showed mitigation in behavioral alterations related to anxiety and memory brought about by PTSD. These effects of OLZ were comparable to that of paroxetine a clinically approved drug for PTSD in terms of biochemical and behavioral assessments indicating its anti-PTSD potential.
['Reddy|Nagannathahalli Ranga|NR|', 'Krishnamurthy|Sairam|S|']
D000818:Animals D019208:Brain-Derived Neurotrophic Factor D053148:Caspase 3 D017362:Cyclic AMP Response Element-Binding Protein D004305:Dose-Response Relationship, Drug D048049:Extracellular Signal-Regulated MAP Kinases D008297:Male D000077152:Olanzapine D011619:Psychotropic Drugs D011897:Random Allocation D051381:Rats D015398:Signal Transduction D013313:Stress Disorders, Post-Traumatic
Olanzapine PTSD BDNF ERK CREB Caspase -3