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      Catecholamine, Indoleamine and Corticosteroid Responses in Mice Bearing Tumors

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          The neurochemical and endocrine responses to inoculation of mice with the murine lymphoma cell line AW5E was studied. This cell line was chosen because it is NK cell lysis resistant and thus does not induce a normal immune response. Immune activation has long been known to be a potent stimulator of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as brain catecholamine and indoleamine metabolism, involving increases in the brain concentrations of catabolites of norepinephrine (NE) and serotonin (5-HT), as well as free tryptophan. Mice injected intravenously with AW5E tumor cells exhibited small increases in plasma corticosterone and hypothalamic NE and 5-HT catabolites one day after injection. There were no significant changes after 6 or 8 days, but a sustained increase in hypothalamic NE and 5-HT metabolism appeared 10 days after injection. There were similar, but more limited changes in the brain stem and prefrontal cortex. On the last day tested (day 14), plasma corticosterone was slightly elevated, as were hypothalamic dopamine, NE and 5-HT catabolites and tryptophan. These results indicate that inoculation with AW5E tumor cells increases brain catecholamine and serotonin metabolism, the hypothalamus being the most sensitive region. The most marked increases occurred in the few days preceding death, and thus may be associated with the pathology of the tumor growth.

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          The role of cytokines in cancer cachexia

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            Virus infection as a stressor: influenza virus elevates plasma concentrations of corticosterone, and brain concentrations of MHPG and tryptophan.

            Balb/c mice were infected with influenza virus PR8 (H1N1) by the intranasal route. At various subsequent times, brain samples were examined for their content of catecholamine and indoleamine metabolites, and plasma corticosterone was measured. Virus infection was associated with a progressive loss of body and thymus weights, and an increase in plasma corticosterone. Spleen weight initially increased then decreased. There were also increases in the cerebral content of free tryptophan throughout the brain, and of MHPG, a major catabolite of norepinephrine, especially prominent in the hypothalamus. Thus influenza virus can be regarded as a stressor because, like behavioral stressors, it activates the hypothalamic-pituitary-adrenal axis, and increases cerebral concentrations of tryptophan and norepinephrine catabolites. These changes resemble those observed following administration of sheep red blood cells and Newcastle disease virus, noninfectious activators of the immune system, suggesting that noradrenergic and HPA activation are common concomitants of antigenic stimulation. The mediator of these effects may be interleukin-1 released by activated macrophages. It should be noted that animals infected with viruses can be expected to exhibit stress-like endocrine and neurochemical changes.
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              Blockade by benzodiazepines of the selective high increase in dopamine turnover induced by stress in mesocortical dopaminergic neurons of the rat.

              The effects of electrical foot shock on the activity of the ascending dopaminergic neurons were estimated in the rat by measuring the changes in DOPAC and DA levels in discrete brain areas. DOPAC and DA levels were estimated with a radioenzymatic method in microdiscs of tissues punched out from serial frontal sections of the brain. A marked rise in the ratio of DOPAC/DA levels resulting from an increase of DOPAC and a decrease of DA levels was found in the cerebral frontal cortex at the end of a 20 min stress. The effect was less pronounced in stress of shorter duration from 3 to 10 min and was only related to a reduction of DA levels. Using the DOPAC/DA ratio as an index of the activity of the neurons, the mesocortical dopaminergic neurons were found to be selectively activated under stress since this ratio was increased in the frontal and cingular cortices but not in limbic structures such as the septum, the amygdala and the nucleus accumbens or in the striatum. Finally, pretreatment of the rats with diazepam (5 mg/kg i.p.) or chlordiazepoxide (10 mg/kg i.p.) prevented the increase in the DOPAC/DA ratio in the frontal cerebral cortex of rats submitted to the 20 min stress.

                Author and article information

                S. Karger AG
                December 2000
                15 December 2000
                : 8
                : 3
                : 107-113
                aDepartment of Pharmacology and Therapeutics and bDepartment of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport, La., USA
                54269 Neuroimmunomodulation 2000;8:107–113
                © 2000 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 48, Pages: 7
                Original Paper


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