Cannabinoid receptor expression and phosphorylation are differentially regulated between male and female cerebellum and brain stem after repeated stress: Implication for PTSD and drug abuse

Recent study demonstrated a close relationship between cerebellum atrophy and symptom severity of pediatric maltreatment-related posttraumatic stress disorder (PTSD). It has also been known that females are more vulnerable than males in developing anxiety disorders after exposure to traumatic stress. The mechanisms are unknown. Because cannabinoid receptors (CB1 and CB2) are neuroprotective and highly expressed in the cerebellum, we investigated cerebellar CB expression in stressed rats. Young male and female Sprague-Dawley rats were given 40 unpredictable electric tail-shocks for 2 h daily on 3 consecutive days. CB1 and CB2 mRNA and protein levels in rat cerebellum and brain stem were determined using quantitative real-time PCR and Western blot, respectively. Two-way ANOVA revealed significant gender and stress effects on cerebellar CB1 mRNA expression, with females and non-stressed rats exhibiting higher CB1 mRNA levels than the males (3 fold, p \u3c 0.01) and stressed rats (30%, p \u3c 0.01), respectively. CB1 and CB2 mRNA levels in brain stem were also greater in female rats than males (p \u3c 0.01, p \u3c 0.05, respectively). Repeated stress increased the level of phosphorylated CB1 receptors, the inactivated CB1, in rat cerebellum (p \u3c 0.01), particularly in female rats as revealed by the significant gender × stress interaction. Thus, repeated severe stress caused greater CB1 mRNA suppression and CB1 receptor phosphorylation in female cerebellum that could lead to increased susceptibility to stress-related anxiety disorders including PTSD

Posttraumatic stress disorder and traumatic stress : from bench to bedside, from war to disaster

War is a tragic event and its mental health consequences can be profound. Recent studies indicate substantial rates of posttraumatic stress disorder and other behavioral alterations because of war exposure. Understanding the psychological, behavioral, and neurobiological mechanism of mental health and behavioral changes related to war exposure is critical to helping those in need of care. Substantial work to encourage bench to bedside to community knowledge and communication is a core component of addressing this world health need

PTSD and traumatic stress : from gene to community and bench to bedside

Individuals and communities are exposed to traumatic events, those that are accidents or naturally occurring and those that are intentional or human made. Although resilience is the expected response, for some, posttraumatic stress disorder may be the outcome. Brain models of PTSD require understanding the phenomenology of the disorder and the brain “break down” that occurs. Among several models, importantly, is the perspective that PTSD is a “forgetting” disorder. Other elements in the onset and triggers of PTSD can identify further models to examine at the bench. New studies of the 5-HT2A receptor, the glucocorticoid receptor, p11, mitochondrial genes and cannabinoids are bringing new perspectives to understanding brain function in PTSD. Effective treatments indicate areas for bench research on the mechanisms of the disorder