Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior

Zuo, Daiying; Zhang, Yahong; Cao, Yue; Wu, Chunfu; Tanaka, Masatoshi; Wu, Yuankui

doi:10.1016/j.lfs.2005.09.022

Cited by 61 publications

(37 citation statements)

References 34 publications

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“…Both acute and chronic dizocilpine treatment are well known to induce changes in locomotor activity and stereotypy. However, there are distinct physiological differences between the two treatments, such as changes in glutamate release (29). Therefore, we chronically treated mice with dizocilpine for 5 days by osmotic minipump (0.2 mg/kg per hour) or by daily i.p.…”

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confidence: 99%

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

Kocerha

Faghihi

López‐Toledano

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

268

218

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cerebral cortex ͉ glutamatergic signaling ͉ regulatory RNA N MDA receptors (NMDA-R) control many executive brain functions, such as working memory, and their dysfunction is implicated in a host of brain disorders (1-4). Notably, hypofunctional NMDA-R signaling, particularly in the prefrontal cortex (PFC), has been implicated in the cognitive and behavioral disturbances characteristic of schizophrenia (5), autism (6, 7), attention deficit hyperactivity disorder (ADHD) (8, 9), mood disorders (10), and other psychiatric illnesses. The cellular mechanisms by which disrupted NMDA-R transmission drives behavioral pathology are still unclear, although several of the major proteins involved in this pathway, such as calcium/calmodulin-dependent protein kinase II (CaMKII) (11), have been identified. In this study, we examine whether neurobehavioral abnormalities associated with NMDA-R hypofunction can be attributed to a novel class of regulatory RNA molecules, microRNAs (miRNAs).miRNAs have attracted much attention as regulators of neuronal development and synaptic plasticity (12-15). Furthermore, psychiatric disorders such as schizophrenia, autism, and Tourette's syndrome are associated with dysregulated levels of miRNAs (16)(17)(18)(19)(20). miRNAs are small (Ϸ22 nt) noncoding transcripts that can control expression of protein-coding mRNAs at the posttranscriptional level (21). Pleiotropic miRNAs can control gene expression by binding to complementary sequences in the 3Ј untranslated region (3Ј UTR) of target mRNA transcripts to facilitate their degradation and/or inhibit their translation (15,22,23). Understanding this layer of gene regulation therefore promises to enrich our knowledge of brain function and pathology. Dizocilpine is a highly selective phencyclidine-like NMDA-R antagonist that can rapidly produce schizophrenia-like behavioral deficits in humans and rodents (24). We examined whether a psychotomimetic dose of dizocilpine (0.5 mg/kg, i.p.) altered miRNA expression in brain regions of C57BL/6 mice, by using miRNA microarray profiling as an initial screening approach. Our analysis was focused on the PFC because of the considerable evidence linking this brain region with behavioral pathology in psychiatric illnesses (19). We extracted the small RNAs from the PFC of the mice 15 min after administration of a single dose of dizocilpine, i.e., a time-point at which dizocilpine-induced behavioral disturbances such as hyperlocomotion and stereotypy are readily observed (25). Of note, there was a robust reduction of miR-219 out of 182 miRNAs detectable by microarray in PFC tissues (Table S1). miR-219 is a conserved miRNA expressed in both rodent and human brains, but not in other tissues (26,27). These data demonstrate that concentrations of a brain-specific miRNA, which may play a role in regulating NMDA-R function, are altered during states of NMDA-R hypofunction.In support of the microarray data, RT-PCR analyses demonstrated that miR-219 levels were significantly reduced by Ϸ50% (a change from an average cycle th...

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mentioning

confidence: 99%

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

Kocerha

Faghihi

López‐Toledano

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

268

218

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“…The system could be therefore be considered 'primed' for an agent such as MK-801 that produces a short term elevation in glutamate release (Lopez-Gil et al, 2007, Zuo et al, 2006. Additionally, an increase in glutamate release would allow for more NMDARs to be in the open state, to which MK-801 preferentially binds (Huettner and Bean, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…MK-801 has been found to increase the efflux of glutamate in key regions associated with schizophrenia, including the prefrontal cortex (PFC) and striatum (Jonkers et al, 2002, Roenker et al, 2012, Zuo et al, 2006. Exposure to acute MK-801 also induces dopamine efflux in these same brain regions, as well in the hippocampus (Kretschmer, 1999, Mathe et al, 1999, Schmidt and Fadayel, 1996, Wedzony et al, 1993b, Whitton et al, 1992.…”

Section: Mk-801mentioning

confidence: 99%

“…Acute administration of MK-801 to rodents' dose-dependently induces hyperlocomotion (Bubser et al, 1992, Kuribara et al, 1992b, Qi et al, 2008, Szabo et al, 2005, Zuo et al, 2006. With repeated administration, MK-801-induced locomotor activity can either become decreased -indicative of a tolerance-like effect -or increased, indicative of sensitisation (Kuribara et al, 1992a.…”

Section: Behavioural Effects Of Mk-801mentioning

confidence: 99%

“…Repeated administration of a high dose of MK-801 leads to a tolerance-like effect to the locomotor-stimulatory effects of MK-801 (Zuo et al, 2006). This behavioural tolerance is associated with a decrease in the stimulatory effects of MK-801 on glutamate release in the PFC (Zuo et al, 2006).…”

Section: Mk-801 Sensitisation and Glutamate Releasementioning

confidence: 99%

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Neural mechanisms of MK-801 induced sensitisation

Lefevre¹

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Behavioural sensitisation describes the progressive and enduring augmentation of a drug-induced response that develops with repeated exposure. Sensitisation is a putative mechanism in the pathophysiology of drug addiction and neuropsychiatric disorders such as schizophrenia. In rodents, drug-induced behavioural sensitisation has been described for several different drug classes. The neural mechanisms underpinning behavioural sensitisation to most drugs of abuse share similarities, such as NMDA receptor (NMDAR) activation, although not all use the same mechanism of action.The NMDAR antagonist MK-801 can inhibit sensitisation to other drugs of abuse. However, MK-801 also produces behavioural sensitisation to its own hyperlocomotor inducing effects, suggesting that MK-801 sensitisation has a distinctive mechanism of action.The overall aim of my thesis was to investigate the neural mechanisms of behavioural sensitisation to MK-801 in rats. First, I established the effect of drug dose, environmental context, length of withdrawal period and rat strain on the ability of repeated intermittent MK-801 administration to induce behavioural sensitisation. MK-801-induced sensitisation was shown to be dependent on the dose of MK-801, length of withdrawal period and the rat strain. Sensitisation however was not modulated by the environmental context in which MK-801 administration occurred.In the established sensitisation paradigm, a functional and molecular analysis of the nucleus accumbens of rats sensitised to MK-801 was undertaken. Ex vivo slice electrophysiology revealed a decrease in the excitatory synaptic strength in the nucleus accumbens of rats sensitised to MK-801. An LC-MS/MS proteomics approach demonstrated that proteins altered by MK-801 sensitisationwere predominately related to functions including calcium signalling and mitochondrial dysfunction.I also probed the role of corticosterone signalling using a pharmacological and physiological approach. Pharmacological antagonism of the glucocorticoid receptor with RU486 was found to facilitate behavioural sensitisation to MK-801, potentially through its augmenting effect on MK-801 induced corticosterone levels. Following on from this experiment, I showed that pharmacological antagonism of the stress-related kappa opioid receptor with nor-Binaltorphimine did not have the same effect as RU486. Lastly, I also used LY354740, a pharmacological agonist of the metabotropic glutamate receptors, as a preliminary investigation into the role of glutamatergic transmission. Stimulation of these receptors however was without effect on MK-801 sensitisation.ii Using a range of approaches I have elucidated some of the neural mechanisms and adaptations associated with behavioural sensitisation to MK-801. These results predominately show that sensitisation to MK-801 differs from the mechanism of sensitisation to other drugs of abuse. This model could prove useful for studying the role of NMDARs in the pathophysiology of drug addiction and schizophrenia.iii

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Effect of intermittent subchronic MK‐801 administration on dopamine synthesis capacity and responsiveness in the prefrontal cortex

Shibata,

Enomoto,

Tsutsumi

et al. 2024

Neuropsychopharm Rep

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AimThe therapeutic potential of N‐methyl‐D‐aspartate glutamate receptor (NMDAR) antagonists, particularly ketamine, in mood disorders, is linked to their modulation of dopamine dynamics in the medial prefrontal cortex (mPFC). However, conflicting effects of distinct NMDAR antagonists, like ketamine and phencyclidine, on mPFC dopamine levels stem from variances in their receptor affinity profiles. This study investigates the impact of intermittent subchronic administration of an NMDAR antagonist on dopamine synthesis capacity and responsiveness within the mPFC, focusing on Dizocilpine (MK‐801), a highly selective NMDAR antagonist.MethodsIn vivo microdialysis and high‐performance liquid chromatography assessed extracellular dopamine levels in the mPFC following subchronic MK‐801 treatment. Locomotor activity was measured using a computed video tracking system.ResultsIntermittent subchronic MK‐801 administration, followed by a 24‐h withdrawal, preserved both dopamine synthesis capacity and responsiveness to MK‐801 challenge in the mPFC. However, altered locomotor activity was observed, deviating from previous findings indicating impaired dopamine synthesis and responsiveness in the mPFC with twice‐daily subchronic NMDAR antagonist treatment.ConclusionThese findings offer crucial biochemical insights into the diverse impacts of NMDAR antagonists on dopamine dynamics and the distinct therapeutic mechanisms associated with ketamine in depression treatment. However, further investigation is imperative to pinpoint potential inconsistencies stemming from variances in drug type, dosage, or administration frequency.

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Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior

Cited by 61 publications

References 34 publications

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

Neural mechanisms of MK-801 induced sensitisation

Effect of intermittent subchronic MK‐801 administration on dopamine synthesis capacity and responsiveness in the prefrontal cortex

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