Activation of
glucocorticoid receptor signaling in the stress response to traumatic events has been implicated in the pathogenesis of stress-associated
psychiatric disorders such as
post-traumatic stress disorder (
PTSD). Elevated startle response and hyperarousal are hallmarks of
PTSD, and are generally considered to evince fear (DSM V). To further examine the efficacy of
corticosterone in treating hyperarousal and elevated fear, the present study utilized a learned helplessness stress model in which rats are restrained and subjected to tail
shock for three days. These stressed rats develop a delayed long-lasting exaggeration of the acoustic startle response (ASR) and retarded
body weight growth, similar to symptoms of
PTSD patients (Myers et al., 2005; Speed et al., 1989). We demonstrate that both pre-stress and post-stress administration of
corticosterone (3 mg/kg/day) mitigates a subsequent exaggeration of the ASR measured 14 days after cessation of the stress protocol. Furthermore, the mitigating efficacy of pre-stress administration of
corticosterone (3 mg/kg/day for three days) appeared to last significantly longer, up to 21 days after the cessation of the stress protocol, in comparison to that of post-stress administration of
corticosterone. However, pre-stress administration of
corticosterone at 0.3 mg/kg/day for three days did not mitigate stress-induced exaggeration of the ASR measured at both 14 and 21 days after the cessation of the stress protocol. In addition, pre-stress administration of
corticosterone (3 mg/kg/day for three days) mitigates the retardation of
body weight growth otherwise resulting from the stress protocol. Congruently, co-administration of the
corticosterone antagonist
RU486 (40 mg/kg/day for three days) with
corticosterone (3 mg/kg/day) prior to stress diminished the mitigating efficacy of the exogenous
corticosterone on exaggerated ASR and stress-retarded
body weight. The relative efficacy of pre versus post administration of
corticosterone and high versus low dose of
corticosterone on stress-induced exaggeration of innate fear response and stress-retarded
body weight growth indicate that exogenous
corticosterone administration within an appropriate time window and dosage are efficacious in diminishing traumatic stress induced pathophysiological processes. Clinical implications associated with the efficacy of prophylactic and therapeutic
corticosterone therapy for mitigating symptoms of
PTSD are discussed, particularly in relation to diminishing hyperarousal and exaggerated innate fear response.