Neuropeptiderge Kontrolle des Stress-assoziierten, einschließlich angstähnlichen Verhaltens durch Arginin-Vasopressin und Oxytocin: Studien unter Verwendung der Brattleboro-Ratte

• Applicant: Professor Dr. Mario Engelmann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 47776124

Recent studies suggest that the structurally related neuropeptides argininevasopressin (AVP) and oxytocin (OXT) substantially contribute to anxiety and anxiety disorders. In this context, the signal function of both neuropeptides as neuromodulators rather than neurotransmitters seems to play an outstanding role. Released from somata and dendrites of magnocellular neurons within the hypothalamic paraventricular nucleus (PVN) AVP and OXT have been suggested to reach other limbic brain areas including septum and – via that way – alter the emotional evaluation of stimuli. The present project is aimed at investigating the neuromodulatory role of AVP and OXT originating from the PVN using AVP deficient Brattleboro rats. Preliminary data suggest that these animals show a reduced anxiety-related behavior on the elevated plus-maze. To reveal a modulatory action of intra- PVN released AVP on this altered behavior, we propose to compensate for the congenital absence of AVP in this nucleus by microdialysis administration of the synthetic peptide in the PVN and septum to simulate endogenous AVP release as well as by treatment with an adeno-associated vector to rescue intra-PVN AVP production/release. Simultaneous administration of an AVP receptor antagonist into the septum will help to further characterize the area(s) of the behaviorally relevant neuropeptide action. The proposed experiments will be performed partly in Budapest (microdialysis and plasma sampling, behavioral testing, adenoviral treatment) and partly in Magdeburg (immunohistochemitry, in situ-hybridization, plasma and microdialysis sample assay).

• DFG Programme: Research Grants
• International Connection: Hungary
• Participating Person: Dr. Dóra Zelena