D-cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus
Portero Tresserra, Marta (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)
Olmo Izquierdo, Nuria del (Universidad CEU San Pablo. Departamento de Ciencias Farmacéuticas y de la Salud)
Martí Nicolovius, Margarita (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)
Guillazo i Blanch, Gemma (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)
Vale Martínez, Anna (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)

Date:	2014
Abstract:	Previous research has demonstrated that systemic D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate receptor (NMDAR), enhances memory processes in different learning paradigms and attenuates mnemonic deficits produced by diverse pharmacological manipulations. In the present study two experiments were conducted in rats to investigate whether DCS administered in the hippocampus may rescue relational memory deficits and improve deficient synaptic plasticity, both induced by an intracerebral injection of the muscarinic receptor antagonist scopolamine (SCOP). In experiment 1, we assessed whether DCS would prevent SCOP-induced amnesia in an olfactory learning paradigm requiring the integrity of the cholinergic system, the social transmission of food preference (STFP). The results showed that DCS (10 μg/site) injected into the ventral hippocampus (vHPC) before STFP acquisition compensated the 24-h retention deficit elicited by post training intra-vHPC SCOP (40μg/site), although it did not affect memory expression in non-SCOP treated rats. In experiment 2, we evaluated whether the perfusion of DCS in hippocampal slices may potentiate synaptic plasticity in CA1 synapses and thus recover SCOP-induced deficits in long-term potentiation (LTP). We found that DCS (50µM and 100µM) was able to rescue SCOP (100µM)-induced LTP maintenance impairment, in agreement with the behavioral findings. Additionally, DCS alone (50 µM and 100 µM) enhanced field excitatory postsynaptic potentials prior to high frequency stimulation, although it did not significantly potentiate LTP. Our results suggest that positive modulation of the NMDAR, by activation of the glycine-binding site, may compensate relational memory impairments due to hippocampal muscarinic neurotransmission dysfunction possibly through enhancements in LTP maintenance.
Grants:	Ministerio de Economía y Competitividad PSI2014-52660-R
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Acetylcholine ; Glutamate ; NMDA receptors ; Muscarinic receptors ; Relational memory ; Synaptic plasticity
Published in:	European neuropsychopharmacology, Vol. 24 núm. 11 (2014) , p. 1798-1807, ISSN 1873-7862

DOI: 10.1016/j.euroneuro.2014.10.002

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