EFFECTS OF ZONISAMIDE TREATMENT ON POST-TRAUMATIC STRESS DISORDER MODEL IN RATS

Post-traumatic stress disorder (PTSD) can cause increase of excitatory neurotransmitters, impaired feedback mechanism of hypothalamus-pituitary-adrenal axis and possible excessive glucocorticoid release. Zonisamide (ZNS), an antiseizure drug, inhibits sodium and calcium channels and affects glutamatergic, GABAergic, dopaminergic, and serotonergic pathways. This study examined the effects of systemically administered ZNS on freezing time, anxiety index and serum brain-derived neurotrophic factor (BDNF) levels in rats with PTSD due to a predatory odor. Twenty-four female Wistar rats were divided into four groups: control, trauma, ZNS and trauma-developed ZNS treatment group. Rats in the trauma and treatment groups were exposed to the predatory odor stress. After seven days, control and trauma groups received saline, while the ZNS and treatment groups received 50 mg/kg ZNS via oral gavage. After thirty minutes, the rats were exposed to the trauma reminder and monitored at the elevated plus maze test. Their blood samples were taken to measure serum BDNF and proBDNF levels. Increased freezing time and anxiety index in the trauma group compared to the control group were suppressed with ZNS administered systemically via oral gavage. Serum proBDNF levels showed a statistically significant increase in the PTSD group compared to the control group; however, there was no significant difference in serum BDNF levels among all groups. Studies on PTSD have shown conflicting levels of neurotrophins. Our data suggest that ZNS may be effective in PTSD and the role of ZNS in PTSD should be investigated at different doses and should be studied at multiple dosages and methods.