Pre-clinical Investigations of Therapeutic Markers Associated with Acute and Chronic Restraint Stress: A Nuclear Magnetic Resonance Based Contrast Metabolic Approach

Abstract

Stress can be defined by two parameters, first the psychological sensing of pressure and second is the body's response. However, the exposure time to stress depicts the biological response produced against it. The effect of acute and chronic restraint stress on anxiety and the production of systemic metabolites were investigated in male Sprague-Dawley (SD) rats. Behavioural test was performed on elevated plus maze (EPM) in conjunction with the statistical analysis that exhibited the habituation during long term exposure to stress when compared with the short-term stress. These behaviour-based changes resulted in interpolated concentration of some serum metabolites like carbohydrates, amino acids and lipids as analysed by NMR. Metabolic analysis along with the multivariate analysis demonstrated that the expression of concentration of metabolites including glutamate, proline, succinate, citrate, and tyrosine is higher in the acute stress than the chronic stress, while glucose and lipids i.e., LDL and VLDL changed in the opposite trends. Thus, the aforesaid study provides an analytical strategy for the characterization of perturbed metabolites induced due to the behavioural modifications in an organism. It may further aid in developing potential therapeutic markers at the metabolic levels which may broaden the treatment options for stress and anxiety related disorders.

Recent advances in anxiety disorders: Focus on animal models and pathological mechanisms

“…Restraint stress is currently the most common model of anxiety. Depending on the duration of restraint, it can be categorized into acute restraint stress (ARS) and chronic restraint stress (CRS) 21 . ARS refers to a restraint stimulus that is given only once and lasts for a relatively short period 21 .…”

“…Depending on the duration of restraint, it can be categorized into acute restraint stress (ARS) and chronic restraint stress (CRS). 21 ARS refers to a restraint stimulus that is given only once and lasts for a relatively short period. 21 CRS refers to a restraint stimulus that is repeated at regular consecutive intervals.…”

“… 21 ARS refers to a restraint stimulus that is given only once and lasts for a relatively short period. 21 CRS refers to a restraint stimulus that is repeated at regular consecutive intervals. In the elevated plus‐maze (EPM) test, males exposed to CRS for 11 days showed higher anxiety‐related behaviors than males exposed to CRS for 22 days, but the same behavior was not observed in females.…”

Acute restraint stress regulates brain DNMT3a and promotes defensive behaviors in male rats

“…A single exposure to traumatic stressors may exaggerate the response to a future stressful event. For example, an acute, single exposure to acute restraint stress (ARS) in the rat induced anxiety-like behaviors manifested by reduced percentage of the number of entries and/or time spent in the open arms of the elevated plus maze [ 4 – 6 ]. Depending on the intensity and frequency of stress, the regulatory function of the HPA axis can be imbalanced and consequently trigger molecular and behavioral changes [ 7 – 9 ], potentially leading to the development of neuropsychopathological conditions such as depression and anxiety [ 10 ], and even post-traumatic stress disorders (PTSD) [ 11 ].…”