Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plastic changes in axon terminals of NA LC neurons following repeated stress and antidepressant treatments were examined using electrophysiological or morphological methods. For stress treatment, rats restrained in a small cage were immersed up to the neck in warm water for 10 min daily. Electrophysiological experiments were performed under urethane anesthesia on the day following the termination of stress treatment. To quantify the density of cortical axon terminals arising in the LC, the percentage of LC neurons activated antidromically from the cerebral cortex was assessed. The percentage of LC neurons showing antidromic response to cortical stimulation was increased in the animals stressed for two weeks but not for one week. Since threshold currents for antidromic activation were not changed by the stress treatment, the observed changes were interpreted as morphological (axonal sprouting) rather than physiological consequences in NA axon terminals of LC neurons. To test the ability of antidepressants to induce the regeneration of central NA axons, local injections of 6-OHDA were made bilaterally into the symmetrical sites of the FC. Two weeks after the 6-OHDA injections, the same cortical site of one hemisphere was infused with the antidepressant MPL, DMI, or MIA, and the corresponding site of the other hemisphere with SAL. The density of glyoxylic acid-induced catecholamine fibers was greater in the cortical hemisphere infused with the antidepressants than that infused with SAL. These findings indicate that repeated mild stress and antidepressant treatments induce sprouting of NA LC axons in the cerebral cortex. Axonal sprouting of LC neurons can explain both the delayed onset of the clinical response to antidepressants and subsensitivity of beta-adrenoceptors following repeated stress and antidepressant treatments, and may be a common mechanism for the clinical efficacy of antidepressant drugs and electroconvulsive shock. Furthermore, the findings suggest the possibility that axonal retraction or degeneration of central NA neurons may be involved, at least in part, in the pathology of clinical depression.
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PMID:Axonal sprouting of noradrenergic locus coeruleus neurons following repeated stress and antidepressant treatment. 166 52

Changes in body weight and taste aversion in the learned helplessness paradigm were examined. In Experiment 1, adult male Sprague-Dawley rats drank saccharin or a control solution, followed by either 100 inescapable shocks or simple restraint. Rats were weighted daily and were tested for saccharin aversion two days after the stress session. Shocked rats gained less weight in the days after stress than restrained controls. Saccharin aversion was apparent only among rats that had consumed saccharin before the stress session. Experiment 2 examined whether control over shock affected body weight or taste aversion. Home-cage controls were included to assess the effects of restraint alone. In addition, the combined effects of shock and a toxin on aversion were studied. Rats drank saccharin solution, followed by escapable or inescapable shock, restraint, or no treatment. Then half of each group was injected with saline; the other half was injected with lithium chloride. As in Experiment 1, shock reduced body weight relative to restraint or no treatment, and shock produced a taste aversion among saline-treated rats. However, shock attenuated the aversion produced by lithium chloride, as did simple restraint. There were no differences in body weight or taste aversion between escapably and inescapably shocked rats. These results suggest a role for stress in the anorexia and weight loss associated with clinical depression and may have implications for theories of learning and learned helplessness.
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PMID:Stressors in the learned helplessness paradigm: effects on body weight and conditioned taste aversion in rats. 285 83

In an attempt to characterize differences among male and female smokers based on past and current alcohol use, we studied patterns of drinking, smoking, caffeine intake, and depression as a function of lifetime history of alcohol dependence and current drinking status in a community sample of current smokers. Subjects were 65 male and 152 female moderate-to-heavy smokers. The CAGE was used to screen for lifetime history of alcohol dependence; current drinking status was classified using self-reported number of alcoholic drinks/week. No significant differences were detected for smoking rate, scores on the Fagerstrom Test for Nicotine Dependence, or either coffee or total caffeine intake. Drinkers with a history of alcohol dependence drank significantly more per week than drinkers with no history, with significant gender differences and interaction effects emerging as well; the phenomenon was particularly pronounced in men. Drinkers of both genders with a history of alcohol dependence scored significantly higher on the Center for Epidemiological Studies-Depression scale, with means exceeding the cutoff of 16 associated with clinical depression. Since comorbidity of depression and alcohol dependence is known to exert a detrimental effect on ability to stop smoking, the number of individuals at risk for smoking cessation treatment failure may be much larger than might be inferred from data based on psychiatric assessments or collected in inpatient settings. Routine screening for depressive symptomatology combined with heavy alcohol use in primary care settings may therefore be helpful in identifying smokers in need of more intensive stop-smoking interventions.
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PMID:Self-reported alcohol use patterns in a sample of male and female heavy smokers. 924 36

A significant proportion of patients suffering from major clinical depression exhibit sudden bursts of anger often described as "panic attacks without anxiety or fear" or "irritability." We investigated aggressive behavior in mice from four different inbred strains subjected to unpredictable chronic mild stress (UCMS). Our results show that UCMS affects self-grooming behavior, as evaluated by the state of an animal's fur, with severity of symptoms differing according to genetic background. Furthermore, UCMS increased aggression both in a resident-intruder test and between cage-mates. UCMS is therefore a valuable model of the problematic aggressive behavior seen in depressive patients.
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PMID:Agonistic behavior and unpredictable chronic mild stress in mice. 1457 28

Fatigue is a common and highly distressing symptom of cancer associated with reduced quality of life and considerable psychological and functional morbidity. The reported prevalence of cancer-related fatigue ranges from 4% to 91%, depending on the specific cancer population studied and the methods of assessment. Cancer-related fatigue has typically been underreported, underdiagnosed, and undertreated. Fatigue and depression may coexist in cancer patients, and considerable overlap of symptoms occurs. This is partly the reason for the interest in examining the role of psychotropic medications in treating fatigue. Clarifying the relationship between depression and fatigue is necessary to effectively evaluate and treat cancer-related fatigue. Even with International Classification of Diseases criteria, differentiating cancer-related fatigue is difficult. Psychotropic drugs that have been studied for cancer-related fatigue include psychostimulants, wakefulness-promoting agents, and antidepressants. Methylphenidate has been studied most and seems to be effective and well tolerated despite common side effects. Some preliminary data support using modafinil in cancer-related fatigue with less concern about tolerance or dependence. Antidepressant studies have shown mixed results. Paroxetine seems to show benefit for fatigue primarily when it is a symptom of clinical depression. Bupropion, a norepinephrine/dopamine reuptake inhibitor, may have psychostimulant-like effects, and therefore may be more beneficial for treating fatigue. However, studies are currently limited. Randomized, placebo-controlled trials with specific agents are needed to further assess the efficacy and tolerability of psychotropic medications in the treatment of cancer-related fatigue.
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PMID:Update on psychotropic medications for cancer-related fatigue. 1805 30

Fatigue is a highly distressing symptom of cancer associated with significant psychological morbidity and reduced quality of life. Cancer-related fatigue (CRF) has been underreported, underdiagnosed, and undertreated. Fatigue and depression may coexist in patients with cancer, and considerable overlap of symptoms often occurs. This has led researchers to examine the role of psychotropic medications to treat fatigue. Psychostimulants, wakefulness-promoting agents, antidepressants, and cholinesterase inhibitors have been studied for CRF treatment. Methylphenidate has been studied most and is effective and well tolerated despite common side effects. Some preliminary data support using modafinil for patients with CRF. Antidepressant studies have shown mixed results. Paroxetine shows benefit for fatigue, primarily when it is a symptom of clinical depression. Bupropion sustained release may have psychostimulant-like effects and, therefore, may be beneficial in treating fatigue. Donepezil, a cholinesterase inhibitor, has shown benefit only in open-label trials. Randomized, placebo-controlled trials with specific agents are needed to further assess the efficacy and tolerability of psychotropic medications in CRF treatment.
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PMID:Pharmacologic treatment options for cancer-related fatigue: current state of clinical research. 1884 22

The C57BL/6 mice were subjected to a chronic combined stress which resulted in the induction of a depressive-like state. The occurrence of a depressive-like state was defined by a decrease in sensitivity to the reward determined by the diminished preference of sweetened solutions over regular drinking water. Such decrease is generally considered as a sign of an unhedonic-like state: one of the key features of clinical depression. Applied here, the paradigm in mice allows unhedonia induction in a subpopulation of stressed animals (54% in the current study); remaining mice are regarded as resilient to stress-induced hedonic deficit. The resilient subgroup is taken, therefore, as a "functional control" for those effects of stress that are not accompanied by development of the stress-induced depressive-like state in mice. The analysis of the mRNA extracted from the hippocampi of stress-subjected and home-cage control mice enabled the assessment of gene expression level of over 13 000 genes. This study showed that unhedonic mice are characterized by an up-regulation of 278 and down-regulation of 174 genes related mostly to the CNS development and functions, inter-cellular interactions and signalling, neurological disorders, apoptosis and behavioural regulation. Resilient animals demonstrated up-regulation of 924 and down-regulation of only 29 genes that control formation of cell assemblies, molecular transport, CNS functioning, neurological disorders and various biochemical reactions. Thus, gene expression profiles in the hippocampus of susceptible vs resilient to stress-induced unhedonia inbred subgroups of animals are strictly distinct in both quantity and quality.
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PMID:[Molecular changes in inbred mice with individual vulnerability vs resilience to stress-induced depressive-like state]. 2196 9

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression have been reported, the unpredictable chronic mild stress (UCMS) protocol is an established translationally-relevant model for inducing behavioral symptoms commonly associated with clinical depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS protocol also induces physiological (e.g., hypercortisolemia, hypertension) and neurological (e.g., anhedonia, learned helplessness) changes that are clinically associated with depression. Importantly, UCMS-induced depressive symptoms can be ameliorated through chronic, but not acute, treatment with common SSRIs. As such, the UCMS protocol offers many advantages over acute stress protocols or protocols that utilize more extreme stressors. Our protocol involves randomized, daily exposures to 7 distinct stressors: damp bedding, removal of bedding, cage tilt, alteration of light/dark cycles, social stresses, shallow water bath, and predator sounds/smells. By subjecting rodents 3-4 hr daily to these mild stressors for 8 weeks, we demonstrate both significant behavioral changes and poor health outcomes to the cardiovascular system. This approach allows for in-depth interrogation of the neurological, behavioral, and physiological alterations associated with chronic stress-induced depression, as well as for testing of new potential therapeutic agents or intervention strategies.
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PMID:An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents. 2665 Jun 68