ORBi: Vignisse Julie - Simultaneous versus solitary pharmacological manipulation of NMDA- and AMPA- receptors: effects of new drugs on contextual learning and its extinction

Reference : Simultaneous versus solitary pharmacological manipulation of NMDA- and AMPA- receptors: ...


	Document type :	Scientific congresses and symposiums : Poster
	Discipline(s) :	Social & behavioral sciences, psychology : Neurosciences & behavior
	To cite this reference:	http://hdl.handle.net/2268/128465

Title :	Simultaneous versus solitary pharmacological manipulation of NMDA- and AMPA- receptors: effects of new drugs on contextual learning and its extinction
Language :	English
Author, co-author :	Vignisse, Julie [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique >]
	Steinbusch, Harry W.M. [Universiteit Maastricht > Department of Neuroscience > School for Mental Health and Neuroscience > >]
	Griegoriev, Vladimir [Russian Academy of Sciences > Institute of Physiologically Active Compounds > > >]
	Bettendorff, Lucien [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique >]
	Bolkunov, Alexei [Russian Academy of Sciences > Institute of Physiologically Active Compounds > > >]
	Nunes, Joao [Lisbon University > Faculty of Sciences > Center of Environmental Biology > >]
	Bachurin, Sergei [Russian Academy of Sciences > Institute of Physiologically Active Compounds > > >]
	Strekalova, Tatyana [Universiteit Maastricht > Department of Neuroscience > School for Mental Health and Neuroscience > >]
Publication date :	17-Jul-2012
Peer reviewed :	No
Audience :	International
Event name :	8th FENS Forum of Neuroscience
Event date :	du 14 au 18 juillet 2012
Event place (city) :	Barcelona
Event country :	Spain
Keywords :	[en] Alzheimer´s disease ; AMPA-receptors ; Dimebon ; fear conditioning ; hippocampus ; memory extinction ; mouse ; NMDA receptor
Abstract :	[en] Both the attenuation of the NMDA-receptor mediated transmission via low affinity blockade mechanism, and the stimulation of AMPA receptor-mediated signaling were shown to result in beneficial neurobiological effects, such as an enhancement of memory and neurogenesis. We aimed to compare the effects of acute pharmacological manipulations of these mechanisms, exerted simultaneously or solely in mice, on learning of two mouse tasks with distinct predominant dependency on either glutamate receptor subtype. In a step-down avoidance task, memantine, low affinity NMDA receptor blocker (5 mg/kg), but not ampakine QQX (5 mg/kg) increased memory scores. In contrast, extinction of contextual fear conditioning was significantly enhanced by the latter, but not by the first drug. Among four new isothiourea derivates used at the doses 0.5-1 mg/kg, one compound that showed a maximal potency with respect to both glutamatergic mechanisms, as well as dimebon (1 mg/kg), had the most prominent memory enhancing effects. Thus, simultaneous low affinity blocade of the NMDA receptor and stimulation of AMPA-mediated transmission can result in eminent pro-cognitive activities. These data point to the importance of multi-target drug mechanism in the regulation of cognitive functions and suggest its potential for clinical implications.
Permalink :	http://hdl.handle.net/2268/128465

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