Search results for "nmda"

Transient oligemia is associated with long-term changes in binding densities of cortical inhibitory GABAA receptors in the rat brain

2009

Recently, we could demonstrate in rats that a short transient oligemic period of only 20-minute duration, induced by systemic hypotension, resulted in a transient decline of spatial memory capacities without any histological damage over a subsequent period of 6 months. In our present study, we checked for more subtle alterations within the highly vulnerable hippocampal CA1 subfield using quantification of neuronal cell density and semi-quantitative analysis of the ischemia-sensitive protein MAP2. Since hippocampal excitatory and inhibitory neurotransmitter receptors are crucially involved in spatial memory processes, quantitative in vitro receptor autoradiography was performed using [(3)H]M…

The effects of nitric oxide on striatal serotoninergic transmission involve multiple targets: an in vivo microdialysis study in the awake rat

2004

Abstract The role of endogenous nitric oxide (NO) in N -methyl- d -aspartate (NMDA)-induced modulation of serotonin (5-HT) release in the striatum of freely moving rats has been studied using microdialysis technique. NMDA-induced increase in 5-HT release was significantly inhibited by selective nitric oxide synthase (nNOS) inhibitor S -methylthiocitrulline (S-Me-TC), ONOO − scavenger l -cysteine ( l -cys), and guanylate cyclase (GC) inhibitor 1 H [1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ). These data suggest that modulation of 5-HT levels is linked to the formation of NO produced by NMDA receptor activation and that endogenously produced NO increases 5-HT concentrations both by stimul…

Role of N-methyl-D-aspartate receptors in the long-term effects of repeated social defeat stress on the rewarding and psychomotor properties of cocai…

2019

Abstract Exposure to social stress increases the vulnerability of experimental animals to the rewarding effects of cocaine and it has been suggested that the glutamatergic system could be involved in these effects of stress. The aim of this work is to determine the role of N-methyl- d -aspartate (NMDA) glutamate receptors in the influence of social stress on the conditioned place preference and locomotor sensitization induced by cocaine. Mice treated with saline or NMDA antagonist memantine (5 or 10 mg/kg) underwent repeated social defeat or were kept in the exploration control condition. After three weeks, all groups (SAL + RSD, M5 + RSD, M10 + RSD, SAL + EXP, M5 + EXP and M10 + EXP) were …

A modeling study suggesting how a reduction in the context-dependent input on CA1 pyramidal neurons could generate schizophrenic behavior.

2011

The neural mechanisms underlying schizophrenic behavior are unknown and very difficult to investigate experimentally, although a few experimental and modeling studies suggested possible causes for some of the typical psychotic symptoms related to this disease. The brain region most involved in these processes seems to be the hippocampus, because of its critical role in establishing memories for objects or events in the context in which they occur. In particular, a hypofunction of the N-methyl-D-aspartate (NMDA) component of the synaptic input on the distal dendrites of CA1 pyramidal neurons has been suggested to play an important role for the emergence of schizophrenic behavior. Modeling st…

Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.

2009

Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits …

NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus

2002

The production of new neurons declines during adulthood and persists, although at very low levels, in the aged hippocampus. Since neurogenesis in young adults has been related to learning and memory, its reduction may contribute to the age-related impairments in these abilities. Adrenalectomy (ADX) enhances neurogenesis in the aged hippocampus, although it also induces neuronal cell death. Since the administration of an NMDA receptor antagonist enhances neurogenesis in young adult rats without deleterious morphological effects, we have tested whether neurogenesis could be reactivated in aged rats. Our study shows that cell proliferation, cell death, neurogenesis and the number of radial gli…

89. Loss of extinction in CA1-NMDA receptor deficient mice: A novel model for PTSD?

2009

S-Ketamine-Induced NMDA Receptor Blockade during Natural Speech Production and Its Implications for Formal Thought Disorder in Schizophrenia: A Pharm…

2017

Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired…

The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency

2018

AbstractAlzheimer’s disease is characterized by intracellular aggregates of hyperphosphorylated tau protein and extracellular plaques of amyloid β peptide, a product of APP processing. The origin of these pathological hallmarks has remained elusive. Here, we have tested the idea that both alterations, at the onset of the disease, may constitute compensatory responses to the same causative and initial trigger, namely NMDA receptor insufficiency. Treatment of rat cortical neurons with the specific NMDA receptor antagonist AP5 within 4 h caused a significant increase in tau phosphorylation at the AT8 and S404 epitopes as well as an increase in APP expression and Aβ 40 secretion. Single intrape…

Pathway-specificity in N-methyl-d-aspartate receptor-mediated synaptic inputs onto subplate neurons

2007

The subplate plays an important role in forming neuronal connections during early cortical development. We characterized by the use of whole-cell and cell-attached patch-clamp recordings in coronal brain slices from newborn mice (postnatal day [P] 0-3) the functional properties of two major pathways onto subplate neurons (SPn), the thalamocortical and the intra-subplate synaptic input. The two afferent pathways were stimulated extracellularly with bipolar electrodes placed in the thalamus and the subplate, respectively. Synaptically evoked and pharmacologically isolated N-methyl-d-aspartate receptor (NMDAR) -mediated responses with an onset latency of approximately 6 ms could be reliably re…