Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress is known to alter GABAergic signaling in the ventral tegmental area (VTA), and this inhibitory plasticity is associated with increased alcohol self-administration. In humans, serotonin 2A receptor (5-HT2AR) agonists can treat stress- and alcohol-related disorders, but the neural substrates are ill-defined. Thus, we reasoned that 5-HT2AR pharmacotherapies may ameliorate the stress-induced dysregulated inhibitory VTA circuitry that contributes to subsequent alcohol abuse. We found that acute stress exposure in mice compromised GABA-mediated inhibition of VTA GABA neurons corresponding with increased ethanol-induced GABAergic transmission. This stress-induced inhibitory plasticity was reversible by applying the 5-HT2AR agonist TCB-2 ex vivo via functional enhancement of the potassium-chloride cotransporter KCC2. The signaling pathway linking 5-HT2AR activation and normalization of KCC2 function was dependent on protein kinase C signaling and phosphorylation of KCC2 at serine 940 (S940), as mutation of S940 to alanine prevented restoration of chloride transport function by TCB-2. Through positive modulation of KCC2, TCB-2 also reduced elevated ethanol-induced GABAergic signaling after stress exposure that has previously been linked to increased ethanol consumption. Collectively, these findings provide mechanistic insights into the therapeutic action of 5-HT2AR agonists at the neuronal and circuit levels of brain reward circuitry.
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PMID:5-HT2A receptor activation normalizes stress-induced dysregulation of GABAergic signaling in the ventral tegmental area. 3180 59

As cases of the coronavirus disease (COVID-19) continue to rise, psychological endurance is a challenge many people will face. For mental health, heightened stress responses to the pandemic, is likely to manifest in three ways: 1) development of a new episode of a disorder in those with a predisposition to a major psychiatric disorder or an acute exacerbation in those who already have such a disorder, 2) development of a trauma or stressor related disorder, such as acute stress disorder, Post Traumatic Stress Disorder (PTSD), or adjustment disorders, and 3) development of a symptomatic stress response that does not meet the diagnostic criteria of a psychiatric disorder. The authors reviewed existing literature on past epidemics, natural disasters, and COVID-19 with a focus on psychiatry and mental health. Psychological effects of past epidemics (Severe Acute Respiratory Syndrome CoV-1, Ebola, Middle East Respiratory Syndrome, the Anthrax threat), past natural disasters, and current COVID-19 data suggest numerous psychological effects following the pandemic. Alcohol use, PTSD, anxiety, anger, fear of contagion, perceived risk, uncertainty, and distrust are a few of the immediate and long-term effects that are likely to result from the COVID-19 pandemic. Identifying people in need of mental health care and determining the appropriate psychiatric services and therapy needed will be important. Increasing the use and availability of telehealth, group meetings, and online resources are some ways that health care workers can prepare for the increasing demand of psychiatric services during and following the pandemic.
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PMID:Past Epidemics, Natural Disasters, COVID19, and Mental Health: Learning from History as we Deal with the Present and Prepare for the Future. 3280 72

Adolescent alcohol use can lead to numerous consequences, including altered stress reactivity and higher risk for later anxiety and alcohol use disorders. Many studies have examined the consequences of heavy ethanol exposure in adolescence, but far less is understood about lower levels of intoxication. The present study examined moderate adolescent ethanol exposure as a possible factor in increasing stress reactivity in adulthood, measured through general and social anxiety-like behaviors, as well voluntary ethanol intake. Male and female Sprague-Dawley rats underwent an adolescent chronic intermittent ethanol (aCIE) vapor exposure during early adolescence, reaching moderate blood ethanol concentrations. Animals then underwent two days of forced swim stress in adulthood. We found that ethanol-exposed males consumed more ethanol than their air counterparts and an interesting stress and ethanol exposure interaction in males. There were no significant effects on voluntary drinking in females. However, the social interaction test revealed increased play-fighting behavior in ethanol-exposed females and reduced social preference in females after two days of stress exposure. Overall, this work provides evidence for sex-specific, long-term effects of moderate aCIE and susceptibility to acute stress in adulthood.
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PMID:Moderate Adolescent Ethanol Vapor Exposure and Acute Stress in Adulthood: Sex-Dependent Effects on Social Behavior and Ethanol Intake in Sprague-Dawley Rats. 3317 57


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