Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors—Relevance to PTSD

Abstract

Lasting anxiogenic effects of predator stress in rodents may model aspects of post traumatic stress disorder (PTSD). There is a link between genetic variation in the serotonin (5-HT) transporter (SERT) and anxiety in humans, prompting the generation of SERT knockout mice. This review brings together studies of SERT knockout male mice, normal female mice, and different 5-HT receptors in predator stress effects on anxiety. These studies provide for a link between vulnerability to the anxiogenic effects of predator stress and abnormalities of 5-HT transmission induced by a life long reduction in 5-HT reuptake in male mice, which creates a vulnerability like that seen in normal female mice. Data reviewed suggest abnormalities in 5-HT transmission contribute to vulnerability to lasting anxiogenic effects of species relevant stressors. To the extent to which predator stress effects model aspects of PTSD, and in the light of relevant human literature, these considerations implicate abnormalities of 5-HT transmission in vulnerability to PTSD per se, and as a potential contributor to enhanced female vulnerability to PTSD.

Predator Stress-Induced CRF Release Causes Enduring Sensitization of Basolateral Amygdala Norepinephrine Systems that Promote PTSD-Like Startle Abnormalities

“…3A), demonstrating that CRF1 receptors in the BLA are required for the development of this stress-induced BLA NE neuroplasticity. Prevention of some long-term effects of a single predator stress have been reported previously with systemic CRF1-R antagonist (Adamec et al, 2010); our present results, for the first time, suggest a possible anatomical site for this phenomenon (the BLA). In contrast, the NEinduced PPI deficit was not altered by the administration of NBI27914 30 min after each ferret exposure ( p Ͻ 0.05 for mock2 vs NE challenge; Fig.…”

“…Because the intent was to model in rats the intense psychogenic stress that is hypothesized to trigger cognitive deterioration in schizophrenia and PTSD (Walker and Diforio, 1997;Yehuda, 2004), a predator stress paradigm was used. This paradigm is considered to capture many of the precipitating features of psychological trauma and is used to study PTSD-like effects in animal models Adamec et al, 2008;Zoladz et al, 2008). Thus, rats (N ϭ 8) with BLA cannulae underwent three exposures to a ferret (one exposure per day); a mock injection into BLA (injectors lowered without infusion) occurred before and after the stress regimen.…”

Resilience against predator stress and dendritic morphology of amygdala neurons

“…Relatively little is known about molecular and neural substrates of such individual differences in coping (47). However correlational behavioral research implicates a variety of possible factors, including personality traits (28;36), interaction of genetic factors and experiential factors, such as reduced functioning polymorphisms in the serotonin transporter (5-HTTLPR), and life stress or social support at the time of stress (4;27;31). Moreover, reactivity of amygdala to environmental threat is modulated by 5-HTTLPR (27) which has also been implicated in PTSD (31;34).…”

Investigating long noncoding RNAs using animal models

“…Gene-environment interactions may unmask unrecognized phenotypes that are important in understanding complex diseases such as psychiatric disorders with known environmental risk factors (110,111). The mechanism of risk conferral for many of these environmental factors, such as exposure to environmental pathogens, maternal stress during pregnancy, or maternal substance abuse during pregnancy, may be investigated by using animal models in a controlled laboratory setting to reveal latent phenotypes and resolve gene-environment interactions ( Figure 3C) (112)(113)(114)(115)(116).…”