Receptive-field plasticity within the auditory neocortex is associated with learning, memory, and acetylcholine (ACh). However, the interplay of elements involved in changing receptive-fields remains unclear. Herein, we describe a depolarizing and a hyperpolarizing potential elicited by repetitive stimulation (20-100 Hz, 0.5-2 sec) and dependent on ACh, which may be involved in modifying recept...

The amygdala plays a critical role in fear conditioning, a model of emotional learning and cue-induced anxiety. In the lateral amygdala, fear conditioning is associated with an enduring increase in synaptic strength mediated through AMPA receptors and with a reduction in paired-pulse facilitation, reflecting an increased probability of neurotransmitter release. Here we show that NMDA-mediated t...

Genetic deletion of NMDA glutamate receptors disrupts development of whisker-related neuronal patterns in the somatosensory system. Independent studies have shown that NMDA receptor antagonists increase cell death among developing neurons. Here, we report that a dramatic feature of the developing somatosensory system in newborn NMDA receptor 1 (NMDAR1) knock-out mice is increased cell death in ...

There has been a great level of enthusiasm to downregulate overactive N-methyl-D-aspartate (NMDA) receptors to protect neurons from excitotoxicity. NMDA receptors play pivotal roles in basic brain development and functions as well as in neurological disorders and diseases. However, mechanistic understanding of antagonism in NMDA receptors is limited due to complete lack of antagonist-bound stru...

Receptor binding assays have shown that diaminodecane (DA-10) reduced binding of open channel blockers to the N-methyl-D-aspartate (NMDA) subtype of postsynaptic glutamate receptor through an interaction with the polyamine regulatory site. Because the action of DA-10 was opposite to that of the polyamine agonist spermine and was reversed by polyamine antagonists, DA-10 has been classified as an...

Background and Objective: N-Methyl-D-aspartate (NMDA) antagonists such as piperidines are the most important antiepileptic drugs. Considering the fact that piperidine derivatives such as phencyclidine (PCP) and its new derivative, 1-[1-(3-methoxyphenyl) (tetralyl)] piperidine (PCP1), have different potencies, the antiepileptic effects of mentioned drugs were investigated in the present study. ...

Recent preclinical data have suggested that glutamate NMDA receptor may be involved in the mechanism of action of antidepressant treatments. Functional antagonists of the NMDA receptor complex exhibit an antidepressant-like effect in animal tests that predict antidepressant activity and in animal models of depression. Zinc, a very potent inhibitor of the NMDA receptor, is active in the forced s...

N-methyl-D-aspartate (NMDA) receptor antagonists show therapeutic potential as neuroprotectants, analgesics, and anticonvulsants. In this context, we used electrical recording techniques to study the in vitro pharmacology of two novel quinoxalinediones, i.e., ACEA-1021 and ACEA-1031 (5-nitro-6,7- dichloro- and 5-nitro-6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione, respectively). Assays with NMDA...

The actions of glutamate in the central nervous system are mediated through interaction with fast activating ionotropic receptors and G protein-coupled metabotropic glutamate receptors (mGluRs). Studies of these receptors have relied on the availability of agonists and antagonists selective for each receptor class. Compounds that were thought to be selective for mGluRs have been extensively use...

Amyloid beta (Aβ) oligomers accumulate in the brain tissue of Alzheimer disease patients and are related to disease pathogenesis. The precise mechanisms by which Aβ oligomers cause neurotoxicity remain unknown. We recently reported that Aβ oligomers cause intracellular Ca(2+) overload and neuronal death that can be prevented by NMDA receptor antagonists. This study investigated whether Aβ oligo...