Acute trauma can lead to life-long changes in susceptibility to psychiatric disease, such as post-traumatic stress disorder (PTSD). Rats given free access to a concentrated glucose solution for 24 h beginning immediately after trauma failed to show stress-related pathology in the learned helplessness model of PTSD and comorbid major depression. We assessed effective dosing and temporal constraints of the glucose intervention in three experiments. We exposed 120 male Sprague-Dawley rats to 100, 1 mA, 3-15 s, inescapable and unpredictable electric tail shocks (over a 110-min period) or simple restraint in the learned helplessness procedure. Rats in each stress condition had access to a 40% glucose solution or water. We measured fluid consumption under 18-h free access conditions, or limited access (1, 3, 6, 18 h) beginning immediately after trauma, or 3-h access with delayed availability of the glucose solution (0, 1, 3, 6 h). We hypothesized that longer and earlier access following acute stress would improve shuttle-escape performance. Rats exposed to traumatic shock and given 18-h access to glucose failed to show exaggerated fearfulness and showed normal reactivity to foot shock during testing as compared to their water-treated counterparts. At least 3 h of immediate post-stress access to glucose were necessary to see these improvements in test performance. Moreover, delaying access to glucose for more than 3 h post-trauma yielded no beneficial effects. These data clearly identify limits on the post-stress glucose intervention. In conclusion, glucose should be administered almost immediately and at the highest dose after trauma.

Post-traumatic stress disorder (PTSD) is a debilitating disease with relatively high lifetime prevalence. It is marked by a high diversity of symptoms and comorbidity with other psychiatric disease. Furthermore, PTSD has a high level of origin and symptom heterogeneity within the population. These characteristics taken together make it one of the most challenging diseases to effectively model in animals. However, with relatively little headway made in developing effective disease interventions, PTSD remains as a high priority target for animal model study. Learned Helplessness (LH) is a procedure classically used to model depression, but has in recent years transitioned to use as a model of PTSD. Animals in this procedure receive 100 inescapable and unpredictable tailshocks or simple restraint without shock. The following day, the animals are tested in a shuttle box, where inescapably-shocked subjects exhibit exaggerated fear and profound deficit in escape performance. Stress-enhanced fear learning (SEFL) also uses an acute (single session) stressor for modeling PTSD in rodents. The SEFL procedure begins with exposure to 15 footshocks or simple context exposure without shock. Animals that initially received the 15 footshocks exhibit future enhanced fear learning. In this review, we will compare the behavior, physiology, and interventions of these two animal models of PTSD. Despite considerable similarity (a single session containing inescapable and uncontrollable shock) the two procedures produce a very divergent set of behavioral consequences.

An acute traumatic event can lead to lifelong changes in stress susceptibility and result in psychiatric disease such as Post-Traumatic Stress Disorder (PTSD). We have previously shown that access to a concentrated glucose solution for 24 h beginning immediately after trauma decreased stress-related pathology in the learned helplessness model of PTSD and comorbid major depression. The current study sought to investigate the peripheral physiological effects of post-stress glucose consumption. We exposed 128 male Sprague-Dawley rats to inescapable and unpredictable 1-milliamp electric tail shocks or simple restraint in the learned helplessness procedure. Rats in each stress condition had access to a 40% glucose solution, 40% fructose solution, or water. Blood and liver tissue were extracted and processed for assay. We assessed corticosterone, corticosteroid-binding globulin (CBG), glucose, and liver glycogen concentrations at various time points following stress. We found that rats given access to glucose following exposure to traumatic shock showed a transient rise in blood glucose and an increase in liver glycogen repletion compared to those that received water or fructose following exposure to electric shock. We also found that animals given glucose following shock exhibited reduced free corticosterone and increased CBG compared to their water-drinking counterparts. However, this difference was not apparent when glucose was compared to fructose. These data suggest that post-stress glucose prophylaxis is likely not working via modulation of the HPA axis, but rather may provide its benefit by mitigating the metabolic challenges of trauma exposure.

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Exposure to traumatic stress leads to persistent, deleterious behavioral and biological changes in both human and non-human species. The effects of stress are not always consistent, however, as exposure to different stressors often leads to heterogeneous effects. The intensity of the stressor may be a key factor in determining the consequences of stress. While it is difficult to quantify intensity for many stress types, electric shock exposure provides us with a stressor that has quantifiable parameters (presentation length x intensity x number = shock volume). Therefore, to test the procedural differences in shock volume that may account for some reported heterogeneity, we used two common shock procedures. Learned helplessness is a commonly reported behavioral outcome, highlighted by a deficit in subsequent shuttle-box escape, which requires a relatively high-volume stress (HVS) of about 100 uncontrollable shocks. Conversely, stress-enhanced fear learning (SEFL) is another common behavioral outcome that requires a relatively moderate-volume stress (MVS) of only 15 shocks. We exposed rats to HVS, MVS, or no stress (NS) and examined the effects on subsequent fear learning and normal weight gain. We found doubly dissociable effects of the two levels of stress. MVS enhanced contextual fear learning but did not impact weight, while HVS produced the opposite pattern. In other words, more stress does not simply lead to greater impairment. We then tested the hypothesis that the different stress-induced sequalae arouse from an energetic challenge imposed on the hippocampus by HVS but not MVS. HVS rats that consumed a glucose solution did exhibit SEFL. Furthermore, rats exposed to MVS and glucoprivated during single-trial context conditioning did not exhibit SEFL. Consistent with the hypothesis that the inability of HVS to enhance fear learning is because of an impact on the hippocampus, HVS did enhance hippocampus-independent auditory fear learning. Finally, we provide evidence that stressors of different volumes produce dissociable changes in glutamate receptor proteins in the basolateral amygdala (BLA) and dorsal hippocampus (DH). The data indicate that while the intensity of stress is a critical determinant of stress-induced phenotypes that effect is nonlinear.