Temporal parameters of post-stress prophylactic glucose treatment in rats

Abstract

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-Stress Fructose and Glucose Ingestion Exhibit Dissociable Behavioral and Physiological Effects

“…Thus, post-stress glucose consumption may allow veridical encoding of the context in the hippocampus, which results in less generalization between the two contexts. This hypothesis is further supported by our previous finding that post-stress glucose only exhibits its prophylactic effects if given within the first three hours of stress pre-treatment [24]. We observed that the glucose-induced transient rise in blood glucose levels occurs three hours post-stress, which suggests that this may play a role in the beneficial effects of glucose consumption.…”

“…Rats were restrained in Plexiglass clear restraining tubes during stress pre-treatment, as previously described [24]. Unscrambled electric shock was administered via electrodes attached to a rat’s extended tail.…”

“…Each restraining tube was housed during the session in an illuminated, sound-attenuating chamber. Testing occurred in a shuttle box, as previously described [24]. A metal barrier divided the shuttle box into equal chambers.…”

“…An alternative explanation is that the prophylactic effects of glucose are independent of glucocorticoid action and merely lie in its ability to prevent the negative metabolic sequelae of trauma. Rats receive inescapable, unpredictable shock transition from an initial anxious reaction to an inactive, depression-like state when exposed to test stimuli [8,9,24]. This state serves as an adaptive mechanism for husbanding limited resources and facilitating the recovery of metabolic homeostasis [11] and is likely mediated by brain adenosine signaling [6,8,9,25].…”

Dissociation in Effective Treatment and Behavioral Phenotype Between Stress-Enhanced Fear Learning and Learned Helplessness

“…This behavior limits the animal's motivation to escape, and is mediated by adenosine signaling in the nucleus accumbens core (Minor et al, 1994a,b, 2001, 2006, 2008, 2010; Plumb et al, 2013). Furthermore, consumption of glucose following the trauma, which has been shown to replete energy reserves (Conoscenti et al, 2019), eliminates the negative behavioral consequences of stress (Minor and Saade, 1997; Conoscenti et al, 2017, 2019). This theory accounts for the transient nature of the behavioral effects, as the effects disappear as the animal recovers from the energy deficit.…”