scholarly journals Role of the NMDA-receptor in Prepulse Inhibition in the Rat

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4260 ◽  
Author(s):  
Klas Linderholm ◽  
Susan Powell ◽  
Elin Olsson ◽  
Maria Holtze ◽  
Ralph Snodgrass ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Prepulse Inhibition ◽  
Kynurenic Acid ◽  
Sensorimotor Gating ◽  
Behavioral Model ◽  
Recognition Site ◽  
Glycine Site ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Cgs 19755

Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan. Studies have revealed increased brain KYNA levels in patients with schizophrenia. Prepulse inhibition (PPI) is a behavioral model for sensorimotor gating and found to be reduced in schizophrenia. Previous studies have shown that pharmacologically elevated brain KYNA levels disrupt PPI in the rat. The aim of the present study was to investigate the receptor(s) involved in this effect. Rats were treated with different drugs selectively blocking each of the sites that KYNA antagonizes, namely the glutamate recognition site of the N-methyl-D-aspartate receptor (NMDAR), the α7* nicotinic acetylcholine receptor (α7nAChR) and the glycine site of the NMDAR. Kynurenine (200 mg/kg) was given to replicate the effects of increased levels of KYNA on PPI. In order to block the glutamate recognition site of the NMDAR, CGS 19755 (10 mg/kg) or SDZ 220–581 (2.5 mg/kg) were administered and to antagonize the α7nAChR methyllycaconitine (MLA; 6 mg/kg) was given. L-701,324 (1 and 4 mg/kg) or 4-Chloro-kynurenine (4-Cl-KYN; 25, 50 and 100 mg/kg), a drug in situ converted to 7-Chloro-kynurenic acid, were used to block the glycine-site of the NMDAR. Administration of SDZ 220-581 or CGS 19755 was associated with a robust reduction in PPI, whereas L-701,324, 4-Cl-KYN or MLA failed to alter PPI. Kynurenine increased brain KYNA levels 5-fold and tended to decrease PPI. The present study suggests that neither antagonism of the glycine-site of the NMDA receptor nor antagonism of the α7nAChR disrupts PPI, rather with regard to the effects of KYNA, blockade of the glutamate recognition-site is necessary to reduce PPI.

scholarly journals NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21)

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Xin Zhang ◽  
Bin Cheng ◽  
Xianghong Jing ◽  
Yongfa Qiao ◽  
Xinyan Gao ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Nmda Receptor ◽  
Ampa Receptor ◽  
Gastrointestinal Motility ◽  
Kynurenic Acid ◽  
Basic Mechanism ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Lines Of Evidence

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

scholarly journals Prepulse Inhibition in HIV-Associated Neurocognitive Disorders

2013 ◽  
Vol 19 (6) ◽  
pp. 709-717 ◽  
Author(s):  
Arpi Minassian ◽  
Brook L. Henry ◽  
Steven Paul Woods ◽  
Florin Vaida ◽  
Igor Grant ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Cognitive Functions ◽  
Sensorimotor Gating ◽  
Neurocognitive Disorders ◽  
Hiv Positive ◽  
Causal Direction ◽  
Cognitively Intact ◽  
Eyeblink Startle ◽  
Hiv Associated Neurocognitive Disorders

AbstractSensorimotor inhibition, or the ability to filter out excessive or irrelevant information, theoretically supports a variety of higher-level cognitive functions. Impaired inhibition may be associated with increased impulsive and risky behavior in everyday life. Individuals infected with HIV frequently show impairment on tests of neurocognitive function, but sensorimotor inhibition in this population has not been studied and may be a contributor to the profile of HIV-associated neurocognitive disorders (HAND). Thirty-seven HIV-infected individuals (15 with HAND) and 48 non-infected comparison subjects were assessed for prepulse inhibition (PPI), an eyeblink startle paradigm measuring sensorimotor gating. Although HIV status alone was not associated with PPI deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI compared to cognitively intact HIV-positive subjects. In HIV-positive subjects, PPI was correlated with working memory but was not associated with antiretroviral therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV accompanies deficits in higher-order cognitive functions, although the causal direction of this relationship requires investigation. Subsequent research on the role of sensorimotor gating on decision-making and risk behaviors in HIV may be indicated. (JINS, 2013, 19, 1–9)

4-Substituted-kynurenic acid derivatives: A novel class of NMDA receptor glycine site antagonists

1997 ◽  
Vol 20 (4) ◽  
pp. 351-357
Author(s):  
Ran Hee Kim ◽  
Yong Jun Chung ◽  
Chang Woo Lee ◽  
Jae Yang Kong ◽  
Young Sik Jung ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Kynurenic Acid ◽  
Glycine Site

The role of stacking interactions in the binding of the NMDA receptor glycine site with antagonists and 3-hydroxykynurenine

BIOPHYSICS ◽  
2008 ◽  
Vol 53 (1) ◽  
pp. 8-14 ◽  
Author(s):  
G. A. Zakharov ◽  
A. V. Popov ◽  
E. V. Savvateeva-Popova ◽  
B. F. Shchegolev
Keyword(s):  
Nmda Receptor ◽  
Stacking Interactions ◽  
Glycine Site

Dorsal striatum D1-expressing neurons are involved with sensorimotor gating on prepulse inhibition test

2017 ◽  
Vol 31 (4) ◽  
pp. 505-513 ◽  
Author(s):  
Samanta Rodrigues ◽  
Cristiane Salum ◽  
Tatiana L Ferreira
Keyword(s):  
Locomotor Activity ◽  
Basal Ganglia ◽  
Prepulse Inhibition ◽  
Startle Response ◽  
Dorsal Striatum ◽  
Sensorimotor Gating ◽  
Reflex Response ◽  
Stimulus Pulse ◽  
D1 And D2 Receptors

Prepulse inhibition (PPI) is a behavioral test in which the startle reflex response to a high-intensity stimulus (pulse) is inhibited by the prior presentation of a weak stimulus (prepulse). The classic neural circuitry that mediates startle response is localized in the brainstem; however, recent studies point to the contribution of structures involved in higher cognitive functions in regulating the sensorimotor gating, particularly forebrain regions innervated by dopaminergic nuclei. The aim of the present study was to verify the role of dorsal striatum (DS) and dopaminergic transmitting mediated by D1 and D2 receptors on PPI test in rats. DS inactivation induced by muscimol injection did not affect PPI (%PPI and startle response), although it impaired the locomotor activity and caused catalepsy. Infusion of D1-like antagonist SCH23390 impaired %PPI but did not disturb the startle response and locomotor activity evaluated immediately after PPI test. D2 antagonist microinjection (sulpiride) did not affect %PPI and startle response, but impaired motor activity. These results point to an important role of DS, probably mediated by direct basal ganglia pathway, on modulation of sensorimotor gating, in accordance with clinical studies showing PPI deficits in schizophrenia, Tourette syndrome, and compulsive disorders – pathologies related to basal ganglia dysfunctions.

NMDA receptor coagonist glycine site: evidence for a role in lateral hypothalamic stimulation of feeding

1997 ◽  
Vol 273 (2) ◽  
pp. R790-R796
Author(s):  
B. G. Stanley ◽  
B. S. Butterfield ◽  
R. S. Grewal
Keyword(s):  
Nmda Receptor ◽  
Binding Site ◽  
Eating Behavior ◽  
Lateral Hypothalamus ◽  
Hypothalamic Stimulation ◽  
Glycine Site ◽  
High Doses ◽  
Feeding Control ◽  
Stimulation Of

To investigate the role of the glycine coagonist binding site on the N-methyl-D-aspartate (NMDA) receptor in feeding control, we injected the glycine site antagonist 7-chlorokynurenic acid (7-CK) into the lateral hypothalamus (LH) of satiated rats before LH injection of NMDA, 7-CK (10-44 nmol) blocked the 6- to 10-g eating response elicited by NMDA. This block was reversed by LH pretreatment with glycine, arguing for a specific action at the glycine site. In contrast to the suppression produced by high doses, 7-CK at 0.1 nmol enhanced NMDA-elicited eating. For examination of behavioral specificity, 7-CK was injected into the LH before kainic acid (KA) or DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). 7-CK at a dose of 0.1 nmol suppressed feeding elicited by KA or AMPA, but at 10 nmol it suppressed eating elicited by AMPA while enhancing eating elicited by KA. Finally, bilateral LH injection of 7-CK effectively suppressed eating produced by fasting. These findings support a role for the NMDA receptor coagonist glycine site in LH regulation of eating behavior.

High-dose glycine impairs the prepulse inhibition measure of sensorimotor gating in humans

2010 ◽  
Vol 25 (12) ◽  
pp. 1632-1638 ◽  
Author(s):  
BV O’Neill ◽  
RJ Croft ◽  
C Mann ◽  
O Dang ◽  
S Leung ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Prepulse Inhibition ◽  
Sensory Information ◽  
Sensorimotor Gating ◽  
High Dose ◽  
Double Blind ◽  
Receptor Modulation ◽  
Treatment Conditions ◽  
Core Deficit ◽  
Final Sample

An impaired capacity to filter or ‘gate’ sensory information is a core deficit in cognitive function associated with schizophrenia. These deficits have been linked in part to N-methyl-d-aspartate (NMDA) receptor dysfunction. An association between high levels of glycine, a positive allosteric modulator of the NMDA receptor, and sensorimotor gating impairments (i.e. prepulse inhibition (PPI) deficit) have been reported in animal models of schizophrenia as well as patients with schizophrenia. This study examined the acute effects of modulating the glycine site of the NMDA receptor (with high-dose glycine) on sensory gating as measured by PPI. Sixteen healthy male subjects (final sample size of 12) participated in a double-blind, placebo-controlled, crossover design in which each subject was tested under two acute treatment conditions separated by at least a 5-day washout period; placebo and 0.8 g/kg glycine. PPI was recorded 45 min post treatment using electromyography of the eye-blink response. Relative to placebo, high-dose glycine significantly impaired sensorimotor gating as demonstrated by a decrease in PPI ( t(11) = −2.983, p < 0.05). Administration of a high dose of glycine is associated with impairments in PPI supporting earlier observations in animals and patients with schizophrenia. This result, when taken together with findings in patients, suggests that high synaptic levels of glycine may have some clinically relevant detrimental effects and suggests a potential dissociation of clinical symptomatology and sensory information processing as a function of NMDA receptor modulation in schizophrenia.

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