The effects of galangin in prepulse inhibition test and experimental schizophrenia models

2021 ◽  
pp. 1-27
Author(s):  
Bilgin Kaygisiz ◽  
Sule Aydin ◽  
Engin Yildirim ◽  
Ahmet Musmul ◽  
Kevser Erol ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Prepulse Inhibition ◽  
Cognitive Deficits ◽  
Acetylcholinesterase Inhibitor ◽  
Acetylcholinesterase Inhibitors ◽  
Antipsychotic Agent ◽  
Flavonoid Compound ◽  
Mk 801 ◽  
Way 100635 ◽  
Brain Acetylcholine

Abstract Objective: Acetylcholinesterase inhibitors are the focus of interest in the management of schizophrenia. We aimed to investigate the effects of acute galangin administration, a flavonoid compound with acetylcholinesterase inhibiting activity, on schizophrenia-associated cognitive deficits in rats and schizophrenia models in mice. Methods: Apomorphine-induced prepulse inhibition (PPI) disruption for cognitive functions, nicotinic, muscarinic and serotonergic mechanism involvement, and brain acetylcholine levels were investigated in Wistar rats. Apomorphine-induced climbing, MK-801-induced hyperlocomotion, and catalepsy tests were used as schizophrenia models in Swiss albino mice. The effects of galangin were compared with acetylcholinesterase inhibitor donepezil, and typical and atypical antipsychotics haloperidol and olanzapine, respectively. Results: Galangin (50,100 mg/kg) enhanced apomorphine-induced PPI disruption similar to donepezil, haloperidol, and olanzapine (p<0.05). This effect was not altered in the combination of galangin with the nicotinic receptor antagonist mecamylamine (1 mg/kg), the muscarinic receptor antagonist scopolamine (0.05 mg/kg), or the serotonin-1A receptor antagonist WAY-100635 (1 mg/kg) (p>0.05). Galangin (50,100 mg/kg) alone increased brain acetylcholine concentrations(p<0.05), but not in apomorphine-injected rats (p>0.05). Galangin (50 mg/kg) decreased apomorphine-induced climbing and MK-801-induced hyperlocomotion similar to haloperidol and olanzapine (p<0.05), but did not induce catalepsy, unlike them. Conclusion: We suggest that galangin may help enhance schizophrenia-associated cognitive deficits, and nicotinic, muscarinic cholinergic and serotonin-1A receptors are not involved in this effect. Galangin also exerted an antipsychotic-like effect without inducing catalepsy and may be considered as an advantageous antipsychotic agent.

scholarly journals Effect of dizocilpine (MK-801) on the working memory of rats on a three-panel runway apparatus

2018 ◽  
Vol 7 (12) ◽  
pp. 2373
Author(s):  
Naveen Kumar ◽  
Navin Budania ◽  
Arka Mondal ◽  
Sana Tafseer ◽  
Siddarth Ahuja ◽  
...  
Keyword(s):  
Working Memory ◽  
Animal Model ◽  
Nmda Receptor ◽  
Animal Models ◽  
Receptor Antagonist ◽  
Cognitive Deficits ◽  
Latency Period ◽  
Nmda Receptor Antagonist ◽  
Memory Errors ◽  
Mk 801

Background: Understanding the processes underlying cognitive functions is a prerequisite to develop strategies for the treatment of cognitive deficits. There is a great need for valid animal models for investigating the cognitive enhancing effects of potential therapeutics. Many studies have investigated animal models of cognitive deficits by using animals treated with compounds that compromise cognitive abilities. Glutamate, an excitatory neurotransmitter and abundantly distributed in the central nervous system is involved in memory processes through N-methyl-d-aspartate (NMDA) receptors. The behavioural consequences of blocking the NMDA receptor provide the rationale for cognitive impairment as an animal model for the cognitive deficits associated with dementia. Authors investigated the effect of dizocilpine (MK-801), an NMDA-receptor antagonist (non-competitive) on the working memory in rats using the three-panel runway apparatus.Methods: Total 24 trained male albino rats were randomly divided into 4 groups of 6 animals each. Varying doses of MK-801 were administered to the animals. Working memory errors and latency periods were evaluated on the three panel Runway apparatus.Results: Treatment with MK-801 at the dose of 0.03mg/ kg did not result in any significant change in working memory errors or latency period in comparison to saline control. MK-801 treatment at dose of 0.1mg/kg and 0.3mg/kg resulted in a significant increase in the number of working memory errors and latency period as compared to control.Conclusions: Authors conclude that MK-801 treatment in the dose of 0.1mg/ kg and 0.3mg/kg resulted in working memory deficits on the three-panel runway apparatus. Rats with cognitive deficits induced by the prototypical N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 may provide a relevant animal model of dementia based on the mechanistic approach of blocking NMDA/glutamatergic signalling.

Glycine and d-serine, but not d-cycloserine, attenuate prepulse inhibition deficits induced by NMDA receptor antagonist MK-801

2008 ◽  
Vol 198 (3) ◽  
pp. 363-374 ◽  
Author(s):  
Nobuhisa Kanahara ◽  
Eiji Shimizu ◽  
Shintaro Ohgake ◽  
Yuko Fujita ◽  
Mami Kohno ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Prepulse Inhibition ◽  
Nmda Receptor Antagonist ◽  
Mk 801

scholarly journals Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

2021 ◽  
Author(s):  
Hong Wei ◽  
Zuyue Chen ◽  
Ari Koivisto ◽  
Antti Pertovaara
Keyword(s):  
Amino Acid ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Gap Junction ◽  
Male Rats ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Mk 801 ◽  
Mechanical Hypersensitivity ◽  
Pain Hypersensitivity

Abstract Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ1 and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (σ1 receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the σ1 and NMDA receptors, and DAAO.

scholarly journals Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver
Keyword(s):  
Nmda Receptor ◽  
Potassium Channel ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Nmda Receptor Antagonist ◽  
Channel Block ◽  
Mk 801 ◽  
Ca1 Region ◽  
Excitatory Transmission ◽  
Ketamine Anesthesia

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

scholarly journals Involvement of 5-HT1AReceptors in the Anxiolytic-Like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Li ◽  
Qian-tong Liu ◽  
Yi Chen ◽  
Jie Liu ◽  
Jin-li Shi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Elevated Plus Maze ◽  
Experimental Models ◽  
Control Group ◽  
Repeated Treatment ◽  
Plus Maze ◽  
Way 100635 ◽  
Marble Burying ◽  
Monoaminergic System ◽  
Light Dark Box

Quercitrin is a well-known flavonoid that is contained in Flos Albiziae, which has been used for the treatment of anxiety. The present study investigated the anxiolytic-like effects of quercitrin in experimental models of anxiety. Compared with the control group, repeated treatment with quercitrin (5.0 and 10.0 mg/kg/day, p.o.) for seven days significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze. In the light/dark box test, quercitrin exerted an anxiolytic-like effect at 5 and 10 mg/kg. In the marble-burying test, quercitrin (5.0 and 10.0 mg/kg) also exerted an anxiolytic-like effect. Furthermore, quercitrin did not affect spontaneous locomotor activity. The anxiolytic-like effects of quercitrin in the elevated plus maze and light/dark box test were blocked by the serotonin-1A (5-hydroxytryptamine-1A (5-HT1A)) receptor antagonist WAY-100635 (3.0 mg/kg, i.p.) but not by theγ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil (0.5 mg/kg, i.p.). The levels of brain monoamines (5-HT and dopamine) and their metabolites (5-hydroxy-3-indoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid) were decreased after quercitrin treatment. These data suggest that the anxiolytic-like effects of quercitrin might be mediated by 5-HT1Areceptors but not by benzodiazepine site of GABAAreceptors. The results of the neurochemical studies suggest that these effects are mediated by modulation of the levels of monoamine neurotransmitters.

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