The Effect of Early Poststressor Intervention with Sertraline on Behavioral Responses in an Animal Model of Post-Traumatic Stress Disorder

Abstract

Whereas several well-controlled studies have established the selective serotonin reuptake inhibitors (SSRIs) as the recommended firstline pharmacotherapeutic agents for acute and chronic post-traumatic stress disorder (PTSD), drug interventions in the acute postexposure phase have not been studied to the same extent and tend to be largely speculative. This study employed an animal model which assesses prevalence of individual stress-response behavior patterns in order to assess the short-term effects of a brief treatment regimen with an SSRI (sertraline) administered immediately after stress-exposure, with those of an identical delayed regimen and of saline. Prevalence rates of rats displaying extreme anxiety-like behavioral responses to predator stress, compared to partial and minimal responses, were assessed in the elevated plus maze and startle response paradigms, with and without intraperitoneal administration of sertraline for 7 days immediately postexposure, or 7 days after exposure. Immediate postexposure administration of sertraline reduced anxiety-like and avoidant behavior, decreased hyperarousal responses and diminished the overall incidence of extreme (PTSD-like) behavioral responses, compared to the delayed treatment regimen and to saline controls. Brief immediate poststress exposure treatment with sertraline reduced prevalence rates of extreme behavioral disruption in the short-term. SSRI drugs are thus worthy of further investigation as agents of secondary prevention in the acute aftermath of stress-exposure.

Animal models of anxiety disorders and stress

“…95 Among proposed models for PTSD, those based on predator exposure have been widely used because they can mimic several symptoms of the disorder, such as hyperarousal and chronic generalized anxiety. [96][97][98] The anxiogenic effects of this procedure are long-lasting, persisting for at least 3 weeks, and reflect the non-associative sensitized fearful manifestations that are observed in PTSD patients. 95 For example, in rats, a single cat exposure modifies the function of brain areas (such as the amygdala, prefrontal cortex, and hippocampus) that have been associated with the genesis of PTSD symptoms in humans.…”

“…99,100 In this model, the animals are exposed to a live cat or its odor for 5-30 min and, after 7 to 21 days, are exposed to an animal model of anxiety such as the EPM, fear conditioning, or startle-potentiated responses. 74,96,98 Psychological and physical stress models Essentially, these models induce stress by exposing the animals to psychological or physical challenges. These procedures may be used in acute or chronic studies depending on the objectives and parameter chosen by the experimenter to evaluate the impact of stress on anxiety.…”

Pharmacological Prevention of Posttraumatic Stress Disorder: A Systematic Review

“…This may reflect the relatively long period between trauma exposure and initiation of treatment in both studies, as discussed above. Given the apparent efficacy of SSRIs in an animal model of PTSD [47], trials of more immediate treatment with these drugs in the aftermath of trauma may be indicated.…”

Altered ratio of proapoptotic and antiapoptotic proteins in different brain regions of female rats in model of post-traumatic stress disorder

“…The stress paradigm was produced by placing the rats on 125 ml of dirty cat litter for 10 min in a plexiglass cage (30 cm X 30 cm X 40 cm).The cat litter had been used for 2 days by the same cat and had been sifted for stools as described previously [17,[19][20][21]. The control animals were exposed to fresh, unused litter for the same amount of time.…”