167 research outputs found
Effects of GPR139 agonism on effort expenditure for food reward in rodent models: Evidence for pro-motivational actions
Apathy, deficiency of motivation including willingness to exert effort for reward, is a common symptom in many psychiatric and neurological disorders, including depression and schizophrenia. Despite improved understanding of the neurocircuitry and neurochemistry underlying normal and deficient motivation, there is still no approved pharmacological treatment for such a deficiency. GPR139 is an orphan G protein-coupled receptor expressed in brain regions which contribute to the neural circuitry that controls motivation including effortful responding for reward, typically sweet gustatory reward. The GPR139 agonist TAK-041 is currently under development for treatment of negative symptoms in schizophrenia which include apathy. To date, however, there are no published preclinical data regarding its potential effect on reward motivation or deficiencies thereof. Here we report in vitro evidence confirming that TAK-041 increases intracellular Ca2+ mobilization and has high selectivity for GPR139. In vivo, TAK-041 was brain penetrant and showed a favorable pharmacokinetic profile. It was without effect on extracellular dopamine concentration in the nucleus accumbens. In addition, TAK-041 did not alter the effort exerted to obtain sweet gustatory reward in rats that were moderately food deprived. By contrast, TAK-041 increased the effort exerted to obtain sweet gustatory reward in mice that were only minimally food deprived; furthermore, this effect of TAK-041 occurred both in control mice and in mice in which deficient effortful responding was induced by chronic social stress. Overall, this study provides preclinical evidence in support of GPR139 agonism as a molecular target mechanism for treatment of apathy
Le catholicisme d´orient et d´occident
Layoutgetreues Digitalisat der Ausg.: Neuchatel [u.a.] : Michaud [u.a.], 1840
Standort: Bibliothek Religionswissenschaft (510)
Signatur: 169
Bemerkungen:
(Bibliothek Wittgenstein
Ueber einige wichtige Fortschritte welche im Maschinenwesen seit dem Anfang dieses Jahrhunderts, besonders in England, gemacht worden sind, und ĂĽber das langsame FortrĂĽcken unsrer Litteratur in diesem Fache
in einer öffentlichen Versammlung der churfürstl. bairischen Akademie der Wissenschaften an ihrer Stiftungsfeyer den 28 März abgelesen von Joseph Baade
Huskisson und die Eisenbahnen : noch ein Wort zu seiner Zeit fĂĽr eine gute Sache
von Joseph von Baade
Franz von Baader's sämmtliche Werke : Systematisch geordnete, durch reiche Erläuterungen von der Hand des Verfassers bedeutend vermehrte, vollständige Ausgabe der gedruckten Schriften sammt dem Nachlasse, der Biographie und dem Briefwechsel
von Franz von Baader. herausgegeben durch einen Verein von Freunden des Verewigte
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