Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated injection of corticosterone (CORT) induces dysregulation in the HPA axis, resulting in depression and anxiety. Many studies have shown that acupuncture, which is widely used for the treatment of stress and mental illness, in East Asian countries, is an effective therapeutic intervention for psychosomatic disorders. We investigated the influence of acupuncture therapy on chronic CORT-induced behavioral responses to the forced swimming test (FST) and elevated plus maze (EPM) and expression of neuropeptide Y (NPY) in the rat brain using immunohistochemistry. Male Sprague-Dawley rats were injected with CORT (40 mg/kg, i.p.) once daily for 19 consecutive days. The dysregulation of HPA axis by external injection of CORT was confirmed by measuring the CORT concentration in plasma and the expression level of CRF in hypothalamus. Acupuncture was performed at the PC6 acupoint for 5 min before CORT injection. Acupuncture significantly reduced depression- and anxiety-like behavior and increased NPY expression in the hypothalamus. These results demonstrated that stimulation of the PC6 acupoint suppresses the symptopathology of the hypoactivated HPA axis in chronic CORT-induced rat model of depression.
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PMID:Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats. 1942 24

Despite adequate antidepressant monotherapy, the majority of depressed patients do not achieve remission. Even optimal and aggressive therapy leads to a substantial number of patients who show minimal and often only transient improvement. In order to address this substantial problem of treatment-resistant depression, a number of novel targets for antidepressant therapy have emerged as a consequence of major advances in the neurobiology of depression. Three major approaches to uncover novel therapeutic interventions are: first, optimizing the modulation of monoaminergic neurotransmission; second, developing medications that act upon neurotransmitter systems other than monoaminergic circuits; and third, using focal brain stimulation to directly modulate neuronal activity. We review the most recent data on novel therapeutic compounds and their antidepressant potential. These include triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, and dopamine receptor agonists. Compounds affecting extra-monoamine neurotransmitter systems include CRF(1) receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Focal brain stimulation therapies include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS).
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PMID:Emerging targets for antidepressant therapies. 1950 41

For studying the role of CRF in the process of depression, chronic intra-cerebral ventricular administration of CRF in normal rats for 21 days were performed and compared with the depression model of chronic unpredictable miled stress (CUMS) in rats. The Open-field Test and Morris water Maze were employed to test the ability of locomotion and learning and memory. HPLC-UV, RT-PCR were employed to analyze the level of blood serum cortisol and the expression of CRF as well as its receptors (R1 and R2) of CUMS models. After chronic stress, the locomotion activity and spatial learning and memory ability decreased obviously, while the level of serum cortisol increased evidently, and the CRF and its receptor-1 mRNA levels were higher compared with those in normal rats. The rats with chronic administration of CRF also consistently decreased the weight gain, locomotion activity and the ability of spatial learning and memory as the CUMS model. This work demonstrates that CRF plays a very important role in the depression genesis and development, sustained elevation of CRF induced by stress may be the chief factor for depression.
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PMID:[Chronic administration of CRF makes depression like changes in rats]. 1953 92

Evidence suggests that corticotropin-releasing factor-1 (CRF(1)) receptor antagonists may offer therapeutic potential for the treatment of diseases associated with elevated levels of CRF such as anxiety and depression. A pyrazinone-based chemotype of CRF(1) receptor antagonists was discovered. Structure-activity relationship studies led to the identification of numerous potent analogues including 12p, a highly potent and selective CRF(1) receptor antagonist with an IC(50) value of 0.26 nM. The pharmacokinetic properties of 12p were assessed in rats and Cynomolgus monkeys. Compound 12p was efficacious in the defensive withdrawal test (an animal model of anxiety) in rats. The synthesis, structure-activity relationships and in vivo properties of compounds within the pyrazinone chemotype are described.
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PMID:Synthesis, structure-activity relationships, and in vivo evaluation of N3-phenylpyrazinones as novel corticotropin-releasing factor-1 (CRF1) receptor antagonists. 1955 37

Corticoliberin (corticotrophin-releasing factor, CRF, CRH) is an active regulator of endocrine, autonomic, and immune functions in stress, as well as a mediator of anxiety, determining the behavioral stress response. The present report describes studies of its action on neuron activity evoked by microstimulation of olfactory cortex slices. Behavioral testing in a T maze was used to select individuals with a passive behavioral strategy from a population of Wistar rats, and the animals were subjected to water immersion. Olfactory cortex slices were prepared 10 days later and evoked focal potentials were recorded on perfusion with medium containing corticoliberin (0.1 microM). Among active rats, 60% of slices retained high excitability after stress, and corticoliberin produced only insignificant reductions in the amplitudes of excitatory potentials in these slices, simultaneously increasing the amplitudes of inhibitory potentials. Low excitability was found in 40% of slices from active stressed rats, and corticoliberin had a significant inhibitory effect in these slices. Addition of corticoliberin to the incubation medium used for slices from passive rats with initially low excitability led to complete blockade of synaptic transmission. These data support the involvement of corticoliberin in the development of depression.
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PMID:Effects of corticoliberin on synaptic transmission in rat olfactory cortex slices in a water immersion model of depression. 1962 Dec 74

(S)-5-Chloro-1-(1-cyclopropylethyl)-3-(2,6-dichloro-4-(trifluoromethyl)phenylamino)pyrazin-2(1H)-one (BMS-665053), a pyrazinone-containing compound, is a potent and selective antagonist of corticotropin-releasing factor receptor-1 (CRF-R1) that showed efficacy in the defensive withdrawal model for anxiety in rats, suggesting its use as a potential treatment for anxiety and depression. In vitro metabolism studies of BMS-665053 in rat and human liver microsomes revealed cytochrome P450-mediated oxidation of the pyrazinone moiety, followed by ring opening, as the primary metabolic pathway. Detection of a series of GSH adducts in trapping experiments suggested the formation of a reactive intermediate, probably as a result of epoxidation of the pyrazinone moiety. In addition, BMS-665053 (20 mg/kg i.v.) underwent extensive metabolism in bile duct-cannulated (BDC) rats. The major drug-related materials in rat plasma were the pyrazinone oxidation products. In rat bile and urine (0-7 h), only a trace amount of the parent drug was recovered, whereas significant levels of the pyrazinone epoxide-derived metabolites and GSH-related conjugates were detected. Further evidence suggested that GSH-related conjugates also formed at the dichloroarylamine moiety possibly via an epoxide or a quinone imine intermediate. Other major metabolites in BDC rat bile and urine included glucuronide conjugates. To reduce potential liability due to metabolic activation of BMS-665053, a number of pyrazinone analogs with different substituents were synthesized and investigated for reactive metabolite formation, leading to the discovery of a CRF-R1 antagonist with diminished in vitro metabolic activation.
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PMID:Comparative biotransformation of pyrazinone-containing corticotropin-releasing factor receptor-1 antagonists: minimizing the reactive metabolite formation. 1983 44

Irritable bowel syndrome (IBS) supports the concept of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. This study investigates the neuroendocrine and psychological responses to the acute physical stress of a lumbar puncture (LP) in women with diarrhea-predominant IBS by assessing central and peripheral HPA activity and affective measures. Blood samples have been collected at baseline and immediately post- and 1 hr following LP from 13 women with IBS and 13 controls. Plasma adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine levels are analyzed. A single measure of cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor (CRF(CSF)) and norepinephrine(CSF) is noted. Affective assessments are used to rate anxiety and depression with the Hospital Anxiety and Depression Scale (HADS) and acute mood state is rated using the Stress Symptom Rating questionnaire (stress, anxiety, anger, arousal). The women with IBS display blunted ACTH and cortisol responses to the LP along with a profile of affective responsiveness suggestive of chronic psychosocial stress, although no CRF(CSF) differences between groups are observed.
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PMID:Hypothalamic--pituitary-- adrenal axis dysregulation in women with irritable bowel syndrome in response to acute physical stress. 1985 23

Lifestyle diseases characterize those diseases whose occurrence is primarily based on the daily habits of people and are a result of an inappropriate relationship of people with their environment. The main factors contributing to lifestyle diseases include bad food habits, physical inactivity, wrong body posture, and disturbed biological clock. A report, jointly prepared by the World Health Organization (WHO) and the World Economic Forum, says India will incur an accumulated loss of $236.6 billion by 2015 on account of unhealthy lifestyles and faulty diet. According to the report, 60% of all deaths worldwide in 2005 (35 million) resulted from noncommunicable diseases and accounted for 44% of premature deaths. What's worse, around 80% of these deaths will occur in low and middle-income countries like India which are also crippled by an ever increasing burden of infectious diseases, poor maternal and perinatal conditions and nutritional deficiencies. According to a survey conducted by the Associated Chamber of Commerce and Industry (ASSOC-HAM), 68% of working women in the age bracket of 21-52 years were found to be afflicted with lifestyle ailments such as obesity, depression, chronic backache, diabetes and hypertension. The study 'Preventive Healthcare and Corporate Female Workforce' also said that long hours and working under strict deadlines cause up to 75% of working women to suffer from depression or general anxiety disorder, compared to women with lesser levels of psychological demand at work. The study cited scientific evidence that healthy diet and adequate physical activity - at least 30 minutes of moderate activity at least five days a week - helped prevent NCDs. In India, 10% of adults suffer from hypertension while the country is home to 25-30 million diabetics. Three out of every 1,000 people suffer a stroke. The number of deaths due to heart attack is projected to increase from 1.2 million to 2 million in 2010. The diet [or lifestyle] of different populations might partly determine their rates of cancer, and the basis for this hypothesis was strengthened by results of studies showing that people who migrate from one country to another generally acquire the cancer rates of the new host country, suggesting that environmental [or lifestyle factors] rather than genetic factors are the key determinants of the international variation in cancer rates. Some of the common diseases encountered because of occupational lifestyle are Alzheimer's disease, arteriosclerosis, cancer, chronic liver disease/cirrhosis, chronic obstructive pulmonary disease (COPD), diabetes, hypertension, heart disease, nephritis/CRF, and stroke. Occupational lifestyle diseases include those caused by the factors present in the vicinity like heat, sound, dust, fumes, smoke, cold, and other pollutants. These factors are responsible for allergy, respiratory and hearing problems, and heat or cold shock. So, A healthy lifestyle must be adopted to combat these diseases with a proper balanced diet, physical activity and by giving due respect to biological clock. Kids spending too much time slouched in front of the TV or PCs, should be encourage to find a physical sport or activity they enjoy. Fun exercises should be encouraged into family outings. A pizza-and-video evening should be replaced for a hike and picnic. Kids who do participate in sport, especially at a high competitive level, can find the pressure to succeed very stressful. To decrease the ailments caused by occupational postures, one should avoid long sitting hours and should take frequent breaks for stretching or for other works involving physical movements.
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PMID:Occupational lifestyle diseases: An emerging issue. 2044 27

Quercetin is a bioflavonoid reported to produce variety of behavioral effects like anxiolytic, antidepressant, etc. Recent gathering evidences indicated that quercetin attenuates stress-induced behavioral and biochemical effects. It also decreases CRF expression in the brain. As CRF is commonly implicated in the high-anxiety and depression, we hypothesized that quercetin may involve CRF in its anxiolytic- and antidepressant-like effects. To support such possibility, we investigated the influence of quercetin on CRF or CRF antagonist (antalarmin) induced changes in social interaction time in social interaction test, and immobility time in forced swim test. Results indicated that quercetin (20-40 mg/kg, p.o.) or antalarmin (2-4 microg/mouse, i.c.v.) dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- and antidepressant-like effect. These effects were comparable with the traditional anxiolytic (diazepam, 1-2mg/kg, i.p.) and antidepressant (fluoxetine, 10-20mg/kg, i.p.) agents. Administration of CRF (0.1 and 0.3 nmol/mouse, i.c.v.) produced just opposite effects to that of quercetin on these parameters. Further, it was seen that pretreatment with quercetin (20 or 40 mg/kg, p.o.) dose dependently antagonized the effects of CRF (0.1 or 0.3 nmol/mouse, i.c.v.) in social interaction and forced swim test. The sub-effective dose of antalarmin (1 microg/mouse) when administered along with the sub-effective dose of quercetin (10mg/kg) produced significant anxiolytic-and antidepressant-like effect. These observations suggest reciprocating role of quercetin on the CRF-induced anxiogenic and depressant-like effects.
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PMID:Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice. 2044 36

Adaptive responding to threatening stressors is of fundamental importance for survival. Dysfunctional hyperactivation of corticotropin releasing factor type-1 (CRF(1)) receptors in stress response system pathways is linked to stress-related psychopathology and CRF(1) receptor antagonists (CRAs) have been proposed as novel therapeutic agents. CRA effects in diverse animal models of stress that detect anxiolytics and/or antidepressants are reviewed, with the goal of evaluating their potential therapeutic utility in depression, anxiety, and other stress-related disorders. CRAs have a distinct phenotype in animals that has similarities to, and differences from, those of classic antidepressants and anxiolytics. CRAs are generally behaviorally silent, indicating that CRF(1) receptors are normally in a state of low basal activation. CRAs reduce stressor-induced HPA axis activation by blocking pituitary and possibly brain CRF(1) receptors which may ameliorate chronic stress-induced pathology. In animal models sensitive to anxiolytics and/or antidepressants, CRAs are generally more active in those with high stress levels, conditions which may maximize CRF(1) receptor hyperactivation. Clinically, CRAs have demonstrated good tolerability and safety, but have thus far lacked compelling efficacy in major depressive disorder, generalized anxiety disorder, or irritable bowel syndrome. CRAs may be best suited for disorders in which stressors clearly contribute to the underlying pathology (e.g. posttraumatic stress disorder, early life trauma, withdrawal/abstinence from addictive substances), though much work is needed to explore these possibilities. An evolving literature exploring the genetic, developmental and environmental factors linking CRF(1) receptor dysfunction to stress-related psychopathology is discussed in the context of improving the translational value of current animal models.
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PMID:Therapeutic utility of non-peptidic CRF1 receptor antagonists in anxiety, depression, and stress-related disorders: evidence from animal models. 2082 81


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