D-cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus

作者：Portero Tresserra Marta; Del Olmo Nuria; Marti Nicolovius Margarita; Guillazo Blanch Gemma; Vale Martinez Anna^*

来源：European Neuropsychopharmacology, 2014, 24(11): 1798-1807.

DOI：10.1016/j.euroneuro.2014.10.002

• Acetylcholine
• Glutamate
• NMDA receptors
• Muscarinic receptors
• Relational memory
• Synaptic plasticity

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 (STEP). The results showed that DCS (10 mu g/site) injected into the ventral hippocampus (vHPC) before STEP acquisition compensated the 24-h retention deficit elicited by post-training intra-vHPC SCOP (40 mu g/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 (50 mu M and 100 mu M) was able to rescue SCOP (100 mu M)-induced LTP maintenance impairment, in agreement with the behavioral findings. Additionally, DCS alone (50 mu M and 100 mu M) 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.

• 出版日期2014-11