17 research outputs found

    Environmental enrichment has no effect on the development of dopaminergic and GABAergic fibers during methylphenidate treatment of early traumatized gerbils

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    It is widely believed, that environmental factors play a crucial role in the etiology and outcome of psychiatric diseases such as Attention-Deficit/Hyperactivity Disorder (ADHD). A former study from our laboratory has shown that both methylphenidate (MP) and handling have a positive effect on the dopaminergic fiber density in the prefrontal cortex (PFC) of early traumatized gerbils (Meriones unguiculatus). The current study was performed to investigate if enriched environment during MP application has an additional influence on the dopaminergic and GABAergic fiber densities in the PFC and amygdala in this animal model

    Disease: A Hitherto Unexplored Constraint on the Spread of Dogs (Canis lupus familiaris) in Pre-Columbian South America

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    Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo

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    In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment

    MicroPET investigation of chronic long-term neurotoxicity from heavy ion irradiation

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    Positron emission tomography (PET) permits imaging of the regional biodistribution and pharmacokinetics of compounds labeled with short-lived positron-emitting isotopes. It has enabled evaluation of neurochemical systems in the living human brain, including effects of toxic substances. MicroPET devices allos studies of the rat brain with a spatial resolution of ∼2 mm. This is much poorer resolution than obtained using ex vivo autoradiography. However, animals need not be euthanized before imaging, so repeat studies are possible. This in principle allows the effects of toxic insults to be followed over the lifetime of an individual animal. We used microPET to evaluate brain metabolic effects of irradiation with high-energy heavy ions (HZE radiation), a component of the space radiation environment, on regional glucose metabolism. A significant fraction of neurons would be traversed by these densely ionizing particles during a Mars mission, and there is a need to estimate human neurological risks of prolonged voyages beyond the geomagnetosphere. Rats were irradiated with56Fe (600 MeV/n) ions at doses up to 240 cGy. At 9 months post-irradiation we did not detect alterations in regional accumulation of the glucose analog [18F]2-deoxy-2-fluoro-D-glucose. This may indicate that damage to the brain from HZE particles is less severe than feared. However, because radiation-induced alterations in some behaviors have been documented, it may reflect insensitivity of baseline cerebral glucose metabolism to HZE radiation. These studies will facilitate design of future studies of chronic, long-term exposure to both therapeutic and abused drugs using microPET
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