Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning

Opioid receptor-like (ORL1) receptor distribution in the rat central nervous system: Comparison of ORL1 receptor mRNA expression with 125 I-[ 14 Tyr]-orphanin FQ binding

The recently discovered neuropeptide orphanin FQ (OFQ), and its opioid receptor-like (ORL1) receptor, exhibit structural features suggestive of the μ, κ, and δ opioid systems. The anatomic distribution of OFQ immunoreactivity and mRNA expression has been reported recently. In the present analysis, we compare the distribution of orphanin receptor mRNA expression with that of orphanin FQ binding at the ORL1 receptor in the adult rat central nervous system (CNS). By using in vitro receptor autoradiography with 125 I-[ 14 Tyr]-OFQ as the radioligand, orphanin receptor binding was analyzed throughout the rat CNS. Orphanin binding sites were densest in several cortical regions, the anterior olfactory nucleus, lateral septum, ventral forebrain, several hypothalamic nuclei, hippocampal formation, basolateral and medial amygdala, central gray, pontine nuclei, interpeduncular nucleus, substantia nigra, raphe complex, locus coeruleus, vestibular nuclear complex, and the spinal cord. By using in situ hybridization, cells expressing ORL1 mRNA were most numerous throughout multiple cortical regions, the anterior olfactory nucleus, lateral septum, endopiriform nucleus, ventral forebrain, multiple hypothalamic nuclei, nucleus of the lateral olfactory tract, medial amygdala, hippocampal formation, substantia nigra, ventral tegmental area, central gray, raphe complex, locus coeruleus, multiple brainstem motor nuclei, inferior olive, deep cerebellar nuclei, vestibular nuclear complex, nucleus of the solitary tract, reticular formation, dorsal root ganglia, and spinal cord. The diffuse distribution of ORL1 mRNA and binding supports an extensive role for orphanin FQ in a multitude of CNS functions, including motor and balance control, reinforcement and reward, nociception, the stress response, sexual behavior, aggression, and autonomic control of physiologic processes. J. Comp. Neurol. 412:563–605, 1999. © 1999 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34456/1/2_ftp.pd

Bis (arylsulfonyl) tetrahydropyridines : application to the synthesis of piperidines

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

"Was gibt es Neues ?" : Comedy-Quiz als Infotainmentformat

Iris AdelbrechtKlagenfurt, Alpen-Adria-Univ., Dipl.-Arb., 2009KB2009 14(VLID)240935

International water trade : legal aspects of access to water

En raison de la croissance démographique mondiale, de l’urbanisation grandissante, du changement climatique et de la multiplication des usages, les ressources en eau se raréfient. Or, un bien rare acquiert une valeur économique importante. En parallèle, le caractère vital de l’eau potable lui confère une singularité rendant sensibles les questions et débats dont elle est l’objet. Le commerce international de l’eau est-il possible ? La réponse n’est pas évidente, d’autant que depuis 2010, un droit fondamental à l’accès à l’eau a été reconnu par l’Assemblée générale de l’ONU et par le Conseil des droits de l’homme. Émerge ici un des enjeux principaux relatifs à l’eau : la reconnaissance dans les textes d’un droit humain à l’accès à l’eau impose en pratique une organisation et une protection efficace de l’accès à l’eau. Pour ce faire, les États requièrent parfois l’aide d’investisseurs étrangers via la conclusion de contrats qui participent alors au commerce international de cette ressource. Or, le commerce international d’une ressource protégée par un droit de l’homme semble paradoxal. L’objet de cette étude est donc d’identifier les acteurs et les types de contrats du commerce international de l’eau, ainsi que les contradictions qui existent entre le droit fondamental à l’accès à l’eau et les intérêts des parties au commerce international. Une fois les conflits identifiés, des solutions de conciliation sont proposées afin de permettre une protection durable de l’accès à l’eau.Because of climate change, world population growth, increasing urbanisation and growing use, water resources are becoming scarce. Now, when goods become scarce, their economic value rises. At the same time, the vital character of drinking water gives it a singularity that heightens the sensitivity of questions and debates about it. Is it possible to have an international trade in water ? The answer is not straightforward, especially since the UN General Assembly and Human Rights Council recognised access to water as an essential human right in 2010. This raises one of the fundamental issues concerning water. Recognition in the texts of access to water as a basic human right requires, in practice, the effective organisation and protection of access to water. States sometimes need the assistance of foreign investors to achieve this, through the signing of contracts that contribute to an international trade in this resource. However, international trade in a resource protected by human rights appears somewhat paradoxical. The aim of this study is therefore to identify the different players and types of contract involved in the international trade in water, and the contradictions that exist between the basic right of access to water and the interests of the participants in the international trade. Once the conflicts have been identified, arbitration solutions are proposed to achieve a long-term protection of the access to water