N-methyl-D-aspartate receptors (NMDARs) are one type of ionotropic glutamate receptors (GluRs) and are heterotetrametric cation channels composed of NMDAR1 (NR1), NMDAR2 (NR2A, 2B, 2C or 2D) and NMDAR3 (NR3A or NR3B) subunits. The main subunits are NR1 and NR2 and their combinations are classified into several diverse forms including NR1/NR1/NR2A/NR2A, NR1/NR1/NR2B/NR2B and NR1/NR1/NR2A/NR2B. N...

Chronic pain is still a basic science and clinical challenge. Unraveling of the neurobiological mechanisms involved in chronic pain will offer novel targets for the development of therapeutic strategies. It is well known that central sensitization in the anterior cingulate cortex (ACC) plays a critical role in initiation, development, and maintenance of chronic pain. However, the underlying mec...

AIMS Tolerance to ethanol-induced inhibition of N-methyl-D-aspartate receptors (NMDARs) is thought to underlie the acute adaptive mechanisms against ethanol. To explore these compensatory upregulating mechanisms of NMDARs, we investigated the expression and phosphorylation of NMDAR subunits in vivo following an acute ethanol treatment. METHODS Male Sprague-Dawley rats were given 4 g/kg ethano...

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that utilize glutamate as a neurotransmitter. A variety of evidence suggests that the release of glutamate then activates N-methyl-D-aspartate (NMDA) receptors within the SCN and triggers a signaling cascade that ultimately leads to phase shifts in the circadian system. In this study, w...

We demonstrate that the NMDA receptor is involved in taste learning in the insular cortex of the behaving rat and describe two facets of this involvement. Blockage of the NMDA receptor in the insular cortex by the reversible antagonist APV during training in a conditioned taste aversion (CTA) paradigm impaired CTA memory, whereas blockage of the NMDA receptor in an adjacent cortex or before a r...

NMDA receptors (NMDAR) are key molecules involved in physiological and pathophysiological brain processes such as plasticity and excitotoxicity. Neuronal activity regulates NMDA receptor levels in the cell membrane. However, little is known on which time scale this regulation occurs and whether the two main diheteromeric NMDA receptor subtypes in forebrain, NR1/NR2A and NR1/NR2B, are regulated ...

N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granu...

Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substi...

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estroge...

Persistent relapse to addictive drugs constitutes the most challenging problem in addiction therapy, and is linked to impaired prefrontal cortex regulation of motivated behaviors involving the nucleus accumbens. Using a rat model of heroin addiction, we show that relapse requires long-term potentiation (LTP)-like increases in synaptic strength in the prefrontal cortex projection to the nucleus ...