Current antipsychotic medications are efficacious for the positive symptoms of schizophrenia. However, there remains a significant unmet need for alternate strategies that could result in improved tolerability and/or efficacy for negative and cognitive symptoms. A growing body of research suggests that NMDA mediated neuronal activity is involved in the etiology of schizophrenia. Glycine binds t...

BACKGROUND Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we furth...

The D-isomer of aspartate is both a substrate for glutamate transporters and an agonist of N-methyl-D-aspartate (NMDA) receptors. To monitor the behavior of these receptors and transporters in intact tissue we synthesized a new photo-labile analogue of D-aspartate, N-[(6-nitrocoumarin-7-yl)methyl]-D-aspartic acid (Ncm-D-aspartate). This compound was photolyzed rapidly (t(1/2)=0.11 micros) by UV...

Patterns of neuronal excitation in complex populations can be mapped anatomically by activating ionotropic glutamate receptors in the presence of 1-amino-4-guanidobutane (AGB), a channel-permeant guanidinium analogue. Intracellular AGB signals were trapped with conventional glutaraldehyde fixation and were detected by probing registered serial thin sections with anti-AGB and anti-amino acid imm...

The effects of several N-methyl-D-aspartate (NMDA) receptorand sigma receptor-related compounds on the discriminative stimulus effects of phencyclidine (PCP) were examined in rats trained to discriminate PCP (1.5 mg/kg, i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. PCP produced a dose-dependent increase in PCP-appropriate responding. A non-competitive NMDA r...

Aripiprazole is a D2-like receptor (D2R) partial agonist with a favourable clinical profile. Previous investigations indicated that acute and short-term administration of aripiprazole had effects on PKA activity, GSK3β-dependent pathways, GABAA receptors, NMDA receptor and CREB1 in the brain. Since antipsychotics are used chronically in clinics, the present study investigated the long-term effe...

PURPOSE To determine pharmacological response of dysiherbaine on cultured Müller cells considering the glutamate receptor functions. Dysiherbaine is a new excitotoxic amino acid, which was recently isolated from the water extract of a certain sponge. SUBJECTS AND METHOD Retinas of adult rabbits were used to prepare the Müller cells. Intracellular calcium ion concentration ([Ca2+]i) analysis w...

The use of multiple loose ligations of the rat sciatic nerve has been proposed as a model for the study of allodynia and hyperalgesia. This pain hypersensitivity results from both an increase in the peripheral and central sensitization. The evidence indicating that the development of neuropathic thermal hyperalgesia and mechanical allodynia requires activation of spinal cord NMDA receptors. NMD...

The use of multiple loose ligations of the rat sciatic nerve has been proposed as a model for the study of allodynia and hyperalgesia. This pain hypersensitivity results from both an increase in the peripheral and central sensitization. The evidence indicating that the development of neuropathic thermal hyperalgesia and mechanical allodynia requires activation of spinal cord NMDA receptors. NMD...

Infection by the human immunodeficiency virus (HIV) can result in debilitating neurological syndromes collectively known as HIV-associated neurocognitive disorders. Although the HIV coat protein gp120 has been identified as a potent neurotoxin that enhances NMDA receptor function, the exact mechanisms for this effect are not known. Here we provide evidence that gp120 activates two separate sign...