Topiramate Attenuates Exaggerated Acoustic Startle in an Animal Model of PTSD

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.