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Objective: The efficacy and safety of atomoxetine, the only licensed non-stimulant pharmacological treatment option for ADHD in Europe, is well investigated in clinical trials, the long-term effects in the developing brain still remain elusive. In vitro studies prove that besides the well-known inhibition of the norepinephrine transporter (NET) atomoxetine acts as a blocker of the N-methyl-D-aspartate (NMDA) receptor. Here we present an in vivo study carried out to investigate atomoxetine’s effect in the maturing rat brain. Methods: Pregnant Crl:SD(CD) rats were treated with atomoxetine (3 mg/kg, i.p.) and sodium chloride (0.9%, i.p.), for the period equivalent to human second to third trimenon of pregnancy. After the end of treatment hippocampus, prefrontal cortex, mesencephalon and striatum from embryos and dams were isolated for analysis of gene expression. Results: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed altered expression of genes of the monoaminergic and glutamatergic system in both embryos and dams. Discussion: This study gives hints that atomoxetine might alter transcriptional regulation of genes of the monoaminergic and glutamatergic system in an age-dependent manner. Conclusion: Atomoxetine alters gene expression in vivo. [ABSTRACT FROM AUTHOR]

The extent of growth stimulation of C3 plants by elevated CO2 is modulated by environmental factors. Under optimized environmental conditions (high light, continuous water and nutrient supply, and others), we analysed the effect of an elevated CO2 atmosphere (700 ppm, EC) and the importance of root-bed size on the growth of tobacco. Biomass production was consistently higher under EC. However, the stimulation was overridden by root-bed volumes that restricted root growth. Maximum growth and biomass production were obtained at a root bed of 15 L at ambient and elevated CO2 concentrations. Starting with seed germination, the plants were strictly maintained under ambient or elevated CO2 until flowering. Thus, the well-known acclimation effect of growth to enhanced CO2 did not occur. The relative growth rates of EC plants exceeded those of ambient-CO2 plants only during the initial phases of germination and seedling establishment. This was sufficient for a persistently higher absolute biomass production by EC plants in non-limiting root-bed volumes. Both the size of the root bed and the CO2 concentration influenced the quantitative cytokinin patterns, particularly in the meristematic tissues of shoots, but to a smaller extent in stems, leaves and roots. In spite of the generally low cytokinin concentrations in roots, the amounts of cytokinins moving from the root to the shoot were substantially higher in high-CO2 plants. Because the cytokinin patterns of the (xylem) fluid in the stems did not match those of the shoot meristems, it is assumed that cytokinins as long-distance signals from the roots stimulate meristematic activity in the shoot apex and the sink leaves. Subsequently, the meristems are able to synthesize those phytohormones that are required for the cell cycle. Root-borne cytokinins entering the shoot appear to be one of the major control points for the integration of various environmental cues into one signal for optimized growth.

Objectives: Recent studies indicate that the selective serotonin reuptake inhibitor (SSRI) fluoxetine is not solely effective by the instant inhibition of the serotonin transporter (SERT) but also by its influence on mitotic and/or apoptotic processes., Methods: To investigate the effects of the compound in vitro, we treated neurons from different brain areas with increasing concentrations of fluoxetine. Additionally, human embryonic kidney (HEK-293) cells and HEK-293 cells stably expressing the SERT were used. Cell viability was quantified by MTT-assay and apoptosis via fluorescence-activated cell-sorting analyses. Fluoxetine's effect on the γ-aminobutyric acid (GABA) receptor was electrophysiologically investigated to test the hypothesis if a GABA-mimetic effect exists that might lead - additionally to the well-known N-methyl-D-aspartate (NMDA)-antagonism - to increased apoptosis in immature neurons., Results: In hippocampal, cortical, and both types of HEK-293 cells, viability decreased and apoptosis increased in a dose-dependent manner (0.5-75 μM). In contrast, in mesencephalic and striatal cells the viability was unchanged or even slightly stimulated up to 20 μM fluoxetine. An anti-apoptotic effect of concentrations below 10 μM was observed in these cells. The GABA(A) receptor was directly activated by fluoxetine., Conclusions: We conclude that fluoxetine affects apoptotic processes independently from SERT expression. Since especially the combined GABA-mimetic and NMDA-antagonistic effects increase apoptosis in developing neuronal cells, whereas both effects are neuroprotective in adult neurons we hypothesise that these mechanisms explain the discrepancy of in vitro and in vivo studies.

Background and Purpose: There is increasing evidence that not only the monoaminergic but also the glutamatergic system is involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Hyperactivity of glutamate metabolism might be causally related to a hypoactive state in the dopaminergic system. Atomoxetine, a selective noradrenaline reuptake inhibitor, is the first non-stimulant approved for the treatment of this disorder. Here we have evaluated the effects of atomoxetine on glutamate receptors in vitro., Experimental Approach: The whole-cell configuration of the patch-clamp technique was used to analyse the effect of atomoxetine on N-methyl-d-aspartate (NMDA) receptors in cultured rodent cortical and hippocampal neurons as well as on NMDA receptors heterologously expressed in human TsA cells., Key Results: Atomoxetine blocked NMDA-induced membrane currents. Half-maximal inhibition emerged at about 3 microM which is in the range of clinically relevant concentrations found in plasma of patients treated with this drug. The inhibition was voltage-dependent, indicating an open-channel blocking mechanism. Furthermore, the inhibitory potency of atomoxetine did not vary when measured on NMDA receptors from different brain regions or with different subunit compositions., Conclusions and Implications: The effective NMDA receptor antagonism by atomoxetine at low micromolar concentrations may be relevant to its clinical effects in the treatment of ADHD. Our data provide further evidence that altered glutamatergic transmission might play a role in ADHD pathophysiology.

The authors of the publication "Population Explosion: the Making of a Vision" state: "During our research in the US our goal was to find out how the problem of 'overpopulation' had become, or better said, been made universal following the Second World War. How was it possible that the view become consensus that population size is determined by state or internationally controlled economic variables and that the future of this planet depended upon an optimal control? Finally, how did contraception or the decision how many children a women bears become a political question? Better said, how did they become part of US foreign policy? Through our research we became acquainted with the development of the contraception of 'overpopulation,' from myth to scientific fact, from the perspective of those who were responsible for this evolution." This publication also includes the authors' conclusions of their study and 32 documents consulted by them. It is an interesting vision on how consensus is created., (full text)