BACKGROUND The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic plasticity in the mesolimbic dopamine (DA) circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA) DA neurons, and its association with drug seeking behaviors, has recently bee...

BACKGROUND Spinal cord N-methyl-D-aspartate (NMDA) receptors are intimately involved in the development and maintenance of central sensitization. However, the mechanisms mediating the altered function of the NMDA receptors are not well understood. In this study the role of phosphorylation of NR1 splice variants and NR2 subunits was examined following hind paw inflammation in rats. We further ex...

Dopamine, via activation of D1 receptors, enhances N-methyl-d-aspartate (NMDA) receptor-mediated responses in striatal medium-sized spiny neurons. However, the role of specific NMDA receptor subunits in this enhancement remains unknown. Here we used genetic and pharmacological tools to dissect the contribution of NR1 and NR2A/B subunits to NMDA responses and their modulation by dopamine recepto...

The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a...

NMDA receptors in mice were mutated by gene targeting to substitute asparagine (N) in position 598 of the NR1 subunit to glutamine (Q) or arginine (R). Animals expressing exclusively the mutated NR1 alleles, NR1(Q/Q) and NR1(-/R) mice, developed a perinatally lethal phenotype mainly characterized by respiratory failure. The dysfunctions were partially rescued in heterozygous mice by the presenc...

N-methyl-d-aspartate (NMDA) receptor activated by glutamate/glycine is located in the kidneys. The NMDA receptor subunit NR1 is increased in damaged renal tissue. This study explored the role of NMDA receptors in ischemia-reperfusion-induced renal dysfunction in rats. With Western blot analysis and renal functional assay, NMDA receptor expression was evaluated, as well as its functional role in...

Cyanide can potentiate N-methyl-D-aspartate receptor-mediated physiological responses in neurons. Here we show that this phenomenon may be attributable to a subunit-specific chemical modification of the receptor directly by the toxin. N-Methyl-D-aspartate (30 microM)-induced whole cell responses in mature (22-29 days in vitro) rat cortical neurons were potentiated nearly 2-fold by a 3-5-min tre...

Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synap...

The NMDA receptor NR1 subunit has four splice variants that differ in their C-terminal, cytoplasmic domain. We investigated the contribution of the C-terminal cassettes, C0, C1, C2, and C2', to trafficking of NR1 in heterologous cells and neurons. We identified an ER retention signal (RRR) in the C1 cassette of NR1, which is similar to the RXR motif in ATP-sensitive K(+) channels (Zerangue et a...

NMDA receptor hypofunction in schizophrenia has been inferred by a large number of clinical and preclinical observations; however, whether and how NMDA receptors are exactly involved in the pathogenesis of schizophrenia are still unknown and subject to interpretation. Here we show, in two independent samples of brains from patients with schizophrenia, a significant decrease in the phosphorylati...