Animal Models of Stress - Current Knowledge and Potential Directions

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Background

Stress, the burden of modern society, is a major predisposing and triggering factor to mood disorders in humans. Stress impairs the correct functioning of important brain regions such as the prefrontal cortex, hippocampus, and amygdala, this was reported both in humans and rodents’ studies. Alterations of the correct functioning, eventually leading to dysfunction, are often the result of stress-related psychiatric disorders, such as major depression. Depression is one of the most prevalent incapacitating psychiatric ailments in the world. It has been estimated to affect 20% of the world population and is characterized by a pervasive low mood, loss of interest in common activities, anhedonia, and withdrawal of interest.

Although depression is a treatable illness, the efficacy of antidepressants is often inconsistent, there are still important side effects, or they take a while (weeks) to produce clinical benefits in the patient. There are drugs that are being tested in the clinical stage, such as LY500307, BPN14770, carbidopa/levodopa, ketamine, and leucine. The search for new drugs, characterized by no side effects, is still necessary when we deal with depression, although we must keep in mind that the time needed from drug discovery to its use in clinics is very long and the process is expensive.

The use of different animal models for research purposes in this field is essential. Murine models have contributed to a better understanding of the neurobiology of this disorder. The alteration of the animals’ mood to produce the depression-induced by stress effect and its impact on their behavior relies on the experimental setup and the different stressors to which the animals are presented to during experiments. Animal models have up to now helped to characterize the neurobiological mechanisms induced by psychosocial stressful experiences such as social defeat stress, maternal separation, chronic unpredictable mild stress, acute restraint stress and repeated forced swim stress.

Not only stress-induced animal models represent an adequate model to investigate the neurobiological underpinnings of this affective disorder, including the underlying circuitry modifications and stress-induced rewiring. Specifically, animal models for stress-induced depression are widely used to investigate alterations in a compromised (depressed) central nervous system as well as for antidepressant drugs’ screening.

In this context, organic compounds such as organic selenium compounds, isoquinoline derivatives, 9-(4-Phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (TAK-137), ceftriaxone, N-propyl-2, 2-diphenyl-2-hydroxyacetamide, minocycline and 7, 8-dihydroxyflavone derivatives have gained attention as attractive therapeutic sources that might be potential compounds to treat diseases such as depression in the long run. These compounds’ beneficial characteristics have increased their charm in the field: antioxidant, anti-inflammatory, neuroprotective, antidepressive – in addition to their low toxicity.

This Research Topic’s aim is to collect the current knowledge and advances in the investigation dealing with the treatment strategies to deal with stress and stressed-induced depression, suggested by different studies, including organic compounds, testing, and experimental readouts. In particular, we would like authors to provide the latest advances and knowledge to treat stress and depression in animal stress models, through an effective behavioral evaluation completed by molecular dosage analysis.

We welcome authors to contribute with all types of articles focusing on:

• In vivo or in vitro studies including the different signaling pathways involved in the antidepressant-like effect of organic compounds in stress models
• Neural circuitry rewiring experimental outputs following chronic stress exposure in animal models
• Effect of organic compounds tested and in test in depression induced by stress animal models

Keywords: antidepressant-like, organic compounds, stress, depression induced by stress models, behavioral

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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