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Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD
Published on: October 10, 2012
Repeated olanzapine treatment mitigates PTSD like symptoms in rats with changes in cell signaling factors
Nagannathahalli Ranga Reddy1, Sairam Krishnamurthy1
1Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, U.P., 221 005, India.
Abstract:
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.
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