Search results for "nmda"
showing 10 items of 147 documents
Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Modulates N-Methyl-d-aspartate (NMDA) Receptor-dependent Intracellular Signaling and NMDA-i…
2013
The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes γ-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pul…
Acamprosate blocks the increase in dopamine extracellular levels in nucleus accumbens evoked by chemical stimulation of the ventral hippocampus.
2003
Recently, we have shown that acamprosate is able to modulate extracellular dopamine (DA) levels in the nucleus accumbens (NAc) and may act as an antagonist of N-methyl-D-aspartate (NMDA) receptors. Neurochemical studies show that chemical stimulation (using NMDA) of the ventral subiculum (vSub) of the hippocampus produces robust and sustained increases in extracellular DA levels in the NAc, an effect mediated through ionotropic glutamate (iGlu) receptors. The present study examines whether acamprosate locally infused in the NAc of rats could block or attenuate the increase in NAc extracellular DA elicited by chemical stimulation (with 5 mM NMDA) of the ventral subiculum of the hippocampus. …
Memantine blocks sensitization to the rewarding effects of morphine
2009
Knowledge regarding the specific brain changes and neural plasticity processes produced by repeated drug exposure may be used to advance the understanding of the neurobiology of addiction in order to design appropriate medications. In the present study, the influence of N-methyl-d-aspartate (NMDA) glutamatergic receptors on sensitization to the motor and rewarding effects of morphine was evaluated. The effects of pre-exposure to saline or 20 mg/kg morphine plus the NMDA receptor antagonist memantine (10 or 20 mg/kg) on motor activity and place conditioning induced by a low dose of morphine (2 mg/kg) were assessed. The dose of 2 mg/kg of morphine was ineffective in mice pre-exposed to saline…
Memantine presents different effects from MK-801 in motivational and physical signs of morphine withdrawal
2003
Adaptive changes in neural systems due to chronic opiate exposure are related to the neural plasticity phenomenon, NMDA receptors being implicated in these processes, e.g. tolerance, dependence or withdrawal. In this work, we investigated the effect of two non-competitive NMDA antagonists, memantine and MK-801, in motivational (Conditioned Place Aversion paradigm, CPA) and physical aspects of morphine withdrawal. After the induction of morphine dependence, animals in which the CPA was studied, received memantine (5 and 10 mg/kg) or MK-801 (0.3-0.006 mg/kg) either during the acquisition (conditioning) or expression (test) phase of this procedure. Both drugs were capable of inhibiting conditi…
D1/D5 modulation of synaptic NMDA receptor currents.
2009
Converging evidence suggests that salience-associated modulation of behavior is mediated by the release of monoamines and that monoaminergic activation of D1/D5receptors is required for normal hippocampal-dependent learning and memory. However, it is not understood how D1/D5modulation of hippocampal circuits can affect salience-associated learning and memory. We have observed in CA1 pyramidal neurons that D1/D5receptor activation elicits a bidirectional long-term plasticity of NMDA receptor-mediated synaptic currents with the polarity of plasticity determined by NMDA receptor, NR2A/B subunit composition. This plasticity results in a decrease in the NR2A/NR2B ratio of subunit composition. Sy…
Functional Synaptic Projections onto Subplate Neurons in Neonatal Rat Somatosensory Cortex
2002
Subplate neurons (SPn) play an important role in the formation of thalamocortical connections during early development and show glutamatergic and GABAergic spontaneous synaptic activity. We characterized these synaptic inputs by performing whole-cell recordings from SPn in somatosensory cortical slices of postnatal day 0-3 rats. At -70 mV, electrical stimulation of the thalamocortical afferents elicited in 68% of the SPn a monosynaptic CNQX-sensitive postsynaptic current (PSC). These fast PSCs were mediated by AMPA receptors, because they were prolonged by cyclothiazide and blocked by GYKI 52466. On membrane depolarization, thalamocortical stimulation elicited in 50% of the cells an additio…
Exogenous t-PA Administration Increases Hippocampal Mature BDNF Levels. Plasmin- or NMDA-Dependent Mechanism?
2014
International audience; Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (r)t-PA administration on brain BDNF metabo…
Neurosteroid modulation of the presynaptic NMDA receptors regulating hippocampal noradrenaline release in normal rats and those exposed prenatally to…
2003
Abstract Prenatal exposure to diazepam (DZ), a positive allosteric modulator of the γ-aminobutyric acidA (GABAA) receptor complex, exerts profound effects that become more evident during puberty and in many cases are sex-specific, suggesting that such exposure interferes with the activity of steroid hormones. Apart from their well known effects on the genome, the reduced metabolites of many steroid hormones also interact directly with membrane receptors, including those for N-methyl- d -aspartate (NMDA). In this study, we compared the effects of several neurosteroids on NMDA receptors from normal rats and those exposed in utero to DZ (1.25 mg/kg per day) from the 14th through the 20th day o…
Indicaxanthin from Opuntia ficus-indica Crosses the Blood–Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Con…
2015
Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/ kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependentl…
Oligodendrocyte precursor cells modulate the neuronal network by activity-dependent ectodomain cleavage of glial NG2.
2014
The role of glia in modulating neuronal network activity is an important question. Oligodendrocyte precursor cells (OPC) characteristically express the transmembrane proteoglycan nerve-glia antigen 2 (NG2) and are unique glial cells receiving synaptic input from neurons. The development of NG2+ OPC into myelinating oligodendrocytes has been well studied, yet the retention of a large population of synapse-bearing OPC in the adult brain poses the question as to additional functional roles of OPC in the neuronal network. Here we report that activity-dependent processing of NG2 by OPC-expressed secretases functionally regulates the neuronal network. NG2 cleavage by the α-secretase ADAM10 yields…