Single prolonged stress: toward an animal model of posttraumatic stress disorder.
Although selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in decreasing posttraumatic stress disorder (PTSD) symptoms, a subgroup of PTSD patients remain chronically symptomatic and maintain conditioned fear responses to traumatic stimuli. In this context, the establishment of an appropriate animal model of PTSD is necessary to promote better understanding of the mechanisms of the disorder and to facilitate the development of more effective therapeutic alternatives to SSRIs. Although no single widely accepted animal model of PTSD has been established to date, the single prolonged stress (SPS) animal model has been partially validated as a model for PTSD. SPS rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior and glucocorticoid negative feedback, and they exhibit the expected therapeutic response to paroxetine on enhanced fear memory. In addition, SPS rats exhibit enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which is alleviated by D-cycloserine. The enhanced consolidation and impaired extinction of fear memory found in SPS rats suggests that this model has additional value because recent studies of PTSD indicate that memory abnormalities are a central feature. In this study, we summarize the behavioral and pathophysiological PTSD-like symptoms in SPS, focusing on memory abnormalities, and evaluate the validity of SPS as an animal model of PTSD.
Yamamoto
Shigeto
S
Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Morinobu
Shigeru
S
Takei
Shiro
S
Fuchikami
Manabu
M
Matsuki
Aya
A
Yamawaki
Shigeto
S
Liberzon
Israel
I
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003523:Cycloserine / Q000494:pharmacology; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology*
D018687:Antidepressive Agents, Second-Generation; D000963:Antimetabolites; D005938:Glucocorticoids; D017374:Paroxetine; D003523:Cycloserine