Abstract
Rationale
Exaggerated acoustic startle is a prominent symptom of post-traumatic stress disorder (PTSD); however, its physiological basis is not well understood, and there are few available treatments. Neurobiological research has suggested that anti-kindling agents and/or glutamate antagonists can attenuate the acoustic startle response (ASR) in animal models. The anticonvulsant topiramate is an AMPA antagonist that also demonstrates potent anti-kindling effects and may, therefore, have promise in treating trauma-enhanced ASR.
Objective
To evaluate the ability of topiramate to attenuate stress-induced increases in ASR in a previously validated animal model of PTSD.
Methods
Male Sprague-Dawley rats (n=36) served as controls or received single prolonged stress (SPS). SPS consisted of 2 h restraint, forced swim and ether anesthesia, then a 7-day “undisturbed” period. Animals then received vehicle, 10 mg/kg or 30 mg/kg of topiramate orally, twice daily for 7 days. ASR was assessed for all animals before and after the study, in light and dark environments.
Results
SPS produced a sustained increase in the ASR in both environments, an effect that was significantly reduced by topiramate. Meanwhile the ASR of control animals remained unaffected by topiramate.
Conclusions
The current results provide one of the few demonstrations of a single stress episode producing sustained enhancement of ASR. In addition, topiramate demonstrates promise in treating exaggerated acoustic startle symptoms in PTSD or other stress-related disorders.
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Acknowledgements
This research was supported by Johnson and Johnson Research Institute. The authors would also like to acknowledge the technical assistance of Brandon Kote and So Jung Min.
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Khan, S., Liberzon, I. Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD. Psychopharmacology 172, 225–229 (2004). https://doi.org/10.1007/s00213-003-1634-4
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DOI: https://doi.org/10.1007/s00213-003-1634-4