China
Africa
Explore chapters and articles related to this topic
The Use of Brain Slices in the Study of Free Radical Actions
Published in Avital Schurr, Benjamin M. Rigor, BRAIN SLICES in BASIC and CLINICAL RESEARCH, 2020
A synaptically evoked NMDA response can be recorded in the hippocampal slice. In the presence of DNQX to block the non-NMDA component of the synaptic potential, and low magnesium to alter the voltage-dependence of the NMDA response such that it is evident at resting membrane potential, an orthodromic stimulus elicits a slow synaptic potential that can be completely blocked by APV, a selective NMDA receptor antagonist.88,89 Under these conditions, concentrations of peroxide that have no direct effect on synaptic potentials but interfere with LTP (0.002%) depress the NMDA-mediated potential (Figure 5). The finding that the reducing agent dithiothreitol can elicit LTP provides further evidence that the redox site can modulate the process.90 These data suggest that this redox site is a likely target for free radical attack.
Transmitter/Receptor Mechanisms in Cardiovascular Control by the NTS: Excitatory Amino Acids, Acetylcholine, and Substance P
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
Recently it has been shown that excitatory amino acids are transmitters in the NTS. Several subtypes of excitatory amino acid receptors have been demonstrated pharmacologically in the NTS (see Table 1 for various agonists and antagonists for these receptors).25-28 These include NMDA, kainic acid, QA/AMPA (termed ionotropic receptors because they are directly coupled to ion channels), and trans-ACPD receptors (termed metabotropic receptors; activation of these receptors results in phosphoinositide hydrolysis, intracellular calcium mobilization, and neuronal depolarization by activation of intracellular second-messenger systems).29 Kynurenate (a broad-spectrum excitatory amino acid receptor antagonist) blocks the ionotropic excitatory amino acid receptors, but not ACPD receptors. AP-7 or AP-5 are considered to be specific antagonists for NMDA while DNQX blocks non-NMDA receptors (kainate and AMPA/quisqualate).29 The role of excitatory amino acids in different reflex mechanisms in the NTS is discussed below.
Glutathione and Glutathione Derivatives: Possible Modulators of Ionotropic Glutamate Receptors
Published in Christopher A. Shaw, Glutathione in the Nervous System, 2018
Réka Janáky, Vince Varga, Zsolt Jenei, Pirjo Saransaari, Simo S. Oja
The slight enhancing effect (20 ± 4 percent, mean ± SD, n = 12) of NMDA observed in 0.1 mM Mg2+ medium in the presence of 50 μM glycine is not discernible in standard Krebs–Ringer–Hepes solution (Table 4). This block is relieved in the presence of GSH, but not GSSG (Janáky et al., unpublished results). The release evoked by 1 mM kainate is enhanced by GSSG (Table 5), but only during the late stimulation phase by GSH. It is inhibited by CNQX and DNQX, NBQX being without effect (Janáky et al. 1997). The release evoked by 0.5 mM AMPA is enhanced by GSSG, GSH being ineffective (Table 5). t-ACPD fails to influence the release of dopamine in all conditions (Janáky et al. 1997).
NBQX attenuates relapse of nicotine seeking but not nicotine and methamphetamine self-administration in rats
Published in The World Journal of Biological Psychiatry, 2021
Jana Ruda-Kucerova, Petra Amchova, Filip Siska, Yousef Tizabi
Notably, there is a large spectrum of AMPA/kainate allosteric modulators or antagonists where their selectivity and pharmacodynamic profiles differ substantially from each other (Lees 2000; Gass and Olive 2008). Even the class of quinoxalinediones ligands has a variable mechanism of action. Thus, DNQX and CNQX also possess weak partial agonists at both AMPA and kainate receptors and may antagonise the NMDA receptor’s glycine site (Kessler et al. 1989). NBQX, on the other hand, seems to be most selective for AMPA receptors, with 30- to 60-fold greater selectivity over kainate receptors (Lees 2000). There is a study showing that CNQX but not NBQX can suppress amphetamine-induced conditioned place preference, which may be explained by the NMDA antagonistic effect of CNQX (Mead and Stephens 1999). Hence, the presumed selectivity of the ligands has to be carefully verified. For example, it may be that the NMDA antagonism is truly responsible for numerous anti-addiction effects of the compounds (Jones et al. 2018). Nonetheless, a role of kainate antagonism against alcohol drinking was also recently suggested (Van Nest et al. 2017). Similarly, the investigation of selective AMPA receptor modulators in drug addiction is worth exploring as a recent study has demonstrated potential antidepressant effects of such ligands in an animal model (Gordillo-Salas et al. 2020).
Effects of low-dose alcohol exposure in adolescence on subsequent alcohol drinking in adulthood in a rat model of depression
Published in The World Journal of Biological Psychiatry, 2021
Filip Siska, Petra Amchova, Daniela Kuruczova, Yousef Tizabi, Jana Ruda-Kucerova
Our finding that treatment with NBQX can transiently decrease alcohol intake in adulthood in OBX rats, confirms an important involvement of the glutamatergic system in alcohol intake, and its interaction with alcohol drinking and depressive-like phenotype (Gómez-Coronado et al. 2018). The involvement of glutamate and its receptors, particularly the ionotropic receptor groups composed of NMDA, AMPA and kainate receptors in alcohol addiction and withdrawal has been well documented (Kalivas 2000; Ayers-Ringler et al. 2016; Scofield et al. 2016; Márquez et al. 2017). Specifically, it has been shown that chronic alcohol exposure elevates the extracellular levels of glutamate in the mesolimbic dopaminergic pathway (Ding et al. 2012; Rao et al. 2015). Moreover, seizures associated with alcohol withdrawals are believed to be triggered by an increase in glutamate transmission, as they can be blocked by NMDA receptor antagonists (Nelson et al. 2005; Rao et al. 2015). In addition, both ketamine and NBQX can reduce alcohol intake in rodent models (Rezvani et al. 2017; Ruda-Kucerova et al. 2018). Cannady et al. (2013) have shown that promotion of alcohol drinking induced by aniracetam (selective positive modulator of AMPA receptors) can be reversed by DNQX, an AMPA receptor antagonist similar to NBQX (Cannady et al. 2013). Other studies using mixed AMPA/kainate receptor antagonists have revealed the potential of these substances in attenuating operant alcohol reinforcement (Stephens and Brown 1999) or cue-induced alcohol-seeking behaviour (Czachowski et al. 2012).