title: Corticosterone mitigates the stress response in an animal model of PTSD.
abstract: 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.
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: Stanley E
authors.initials: SE
authors.lastname: Smerin
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xing
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: David
authors.initials: D
authors.lastname: Benedek
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ursano
authors.affiliation: Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Service University of Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. Electronic address: he.li@usuhs.edu.
authors.forename: He
authors.initials: H
authors.lastname: Li
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003345:Corticosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000523:psychology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D003345:Corticosterone
keywords: Amygdala; Corticosterone; Glucocorticoids; Hypothalamus; Stress; Traumatic stress response