An updated animal model capturing both the cognitive and emotional features of post-traumatic stress disorder (PTSD)

Abstract

The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines post-traumatic stress disorder (PTSD) as a “trauma and stressor-related disorder”. PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e., social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffering effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets of the pathology.

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

“…Thus, in agreement with these reports, we reasoned that a habituation-test paradigm would reduce confounding factors associated with novelty (Pawlak et al, 2008; Schneider et al, 2011). Further, re-exposure to behavioral testing was intended to measure key aspects of emotional memories associated with PTSD (Berardi et al, 2014). In particular, we intended to investigate those behaviors associated with aversion, anxiety, fear, and context generalizations.…”

Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats

“…The PTSD model we first described (Berardi et al, 2014) was adapted for the assessment of memory extinction.…”

“…We recently proposed a footshock-based paradigm able to mimic both the enduring cognitive and emotional facets of PTSD pathology useful to model the extinction-based exposure therapy combined with pharmacological treatment (Berardi et al, 2014). The main purpose of the present study was to evaluate the effects of pharmacological manipulation of the endocannabinoid system in a preclinical model of PTSD, by targeting extinction learning processes.…”

“…The main purpose of the present study was to evaluate the effects of pharmacological manipulation of the endocannabinoid system in a preclinical model of PTSD, by targeting extinction learning processes. To this aim, we first adapted our model (Berardi et al, 2014) by including multiple extinction sessions and we verified whether the extinction procedure alone was able to improve the behavioral alterations displayed by traumatized rats. We also evaluated the effects induced by trauma exposure on AEA and 2-AG levels in brain regions critically involved in extinction and emotional behavior, ie, hippocampus, prefrontal cortex, and amygdala (Furini et al, 2014).…”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…Oxytocin release that was independent of mating was involved in the buffering of stress-induced increases in anxiety-like behaviors and circulating corticosterone that occur in female prairie voles if the male partner is present 212 . Furthermore, social buffering in rats was also shown to protect from the development of alterations in social interactions that otherwise emerge following stress exposure 213 . Social buffering by mothers and peers can also protect against effects induced by early-life stress.…”