Methylphenidate Enhances Inhibitory Synaptic Transmission by Increasing the Content of Norepinephrine in the Locus Coeruleus of Juvenile Rats

Kidani, Yuri; Ishimatsu, Masaru; Akasu, Takashi

doi:10.2739/kurumemedj.57.29

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…Methylphenidate appears to enhance inhibitory synaptic transmission in the locus ceruleus in juvenile rats [38]. Since it has been reported that local GABAergic interneurons might play a role gating locus ceruleus function [39], the major brain region for noradrenergic transmission, it is intriguing to speculate that GABA A receptors are downregulated in the locus ceruleus, as has been reported in several other brain regions in FXS [16].…”

Section: Discussionmentioning

confidence: 95%

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

2011

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Hyperactivity, hypersensitivity to auditory stimuli, and exaggerated fear are common behavioral abnormalities observed in individuals with fragile X syndrome (FXS), a neurodevelopmental disorder that is the most common genetic cause of autism. Evidence from studies of the Fmr1 knockout (KO) mouse model of FXS supports the notion that impaired GABAergic transmission in different brain regions such as the amygdala, striatum or cerebral cortex is central to FXS behavioral abnormalities. This suggests that the GABAergic system might be an intriguing target to ameliorate some of the phenotypes in FXS. Our recent work revealed that THIP (gaboxadol), a GABA_A receptor agonist, can restore principal neuron excitability deficits in the Fmr1 KO amygdala, suggesting that THIP may also restore some of the key behavioral abnormalities in Fmr1 KO mice. Here, we reveal that THIP significantly attenuated hyperactivity in Fmr1 KO mice, and reduced prepulse inhibition in a volume-dependent manner. In contrast, THIP did not reverse the deficits in cued fear or startle response. Thus, this study shows that enhancing GABAergic transmission can correct specific behavioral phenotypes of the Fmr1 KO mouse further supporting that targeting the GABAergic system, and specifically tonic inhibition, might be important for correcting or ameliorating some key behaviors in FXS.

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Section: Discussionmentioning

confidence: 95%

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

2011

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“…2B/2C-adrenoceptors in locus coeruleus neurons (Ishimatsu et al 2002). In a later study, whole-cell patch-clamp recordings revealed that MPH enhances inhibitory synaptic transmission by increasing the concentration of NE at noradrenergic synapses in juvenile rat locus coeruleus neurons (Kidani et al 2010). On the other hand, in the dopaminergic neurons originating from the ventral tegmental areas, Prieto-Gomez and colleagues hypothesised after electrophysiological study on brain slices that psychostimulants sensitisation could be involved, though both N-Methyl-D-aspartate (NMDA) and kainite/AMPA glutamate receptors medicated the excitability of these neurons (Prieto-Gomez et al 2004;.…”

Section: Drug Binding and Transport Inhibitionmentioning

confidence: 99%

In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder

Grünblatt

Bartl²,

Marinova

et al. 2012

J Neural Transm

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Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children and adolescents, with up to 5 % affected worldwide. Twin and family studies on ADHD show its high familiality with heritability estimated around 70 %, but, to date, no specific polymorphism or gene was found to be specifically affected. Psychostimulants (amphetamine, methylphenidate) and non-psychostimulants (atomoxetine) are used successfully in ADHD therapy, but many of their mechanisms of action and their adverse effects are not yet fully understood. Therefore, both genetic findings and therapeutic interventions should be further investigated. One easy platform for such studies is in vitro analyses, which encompass neuronal cell culture studies, transfections of genetic constructs, binding and electrophysiology analyses. In this review, different methods will be referred in particular to ADHD findings, and new techniques will be mentioned for future studies of drug or genetic effects in vitro. DOI: https://doi.org/10.1007/s00702-012-0869-9Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-74484 Accepted Version Originally published at: Grünblatt, Edna; Bartl, Jasmin; Marinova, Zoya; Walitza, Susanne (2013). In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder. Journal of Neural Transmission, 120 (1)

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Locus coeruleus neuronal activity correlates with behavioral response to acute and chronic doses of methylphenidate (Ritalin) in adolescent rats

2017

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The objective of this study is to gain insight into the behavioral and neuronal changes induced by acute and chronic methylphenidate (MPD) administration. Specifically, there is limited knowledge of the effects of MPD on the locus coeruleus (LC), the main site of norepinephrine synthesis in the brain. In this study, LC neuronal firing rate was recorded simultaneously with locomotor activity in freely moving adolescent rats. Adolescent rats were chosen to mimic the age group in humans most affected by MPD exposure. Following acute dose of 0.6, 2.5 or 10 mg/kg MPD, all rats showed an increase in locomotor activity. However, in response to chronic MPD doses, individual rats showed either a further increase or decrease in their locomotor activity as compared to the effect initiated by the acute dose-expressing either behavioral sensitization or tolerance, respectively. The LC neuronal recordings from animals expressing behavioral sensitization showed that the majority of units responded to chronic MPD exposure by further increasing firing rates as compared to the initial response to the acute MPD exposure. For the LC neuronal units recorded from animals expressing behavioral tolerance, however, the majority of the units responded to chronic exposure by attenuating or no significant effect on their firing rate as compared to the acute MPD exposure. This observation indicates a correlation between the LC neuronal responses and behavioral activity to chronic MPD exposure. The study shows that LC participates in the effect of MPD and the behavioral expression of sensitization and tolerance to chronic exposure of MPD.

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Methylphenidate Enhances Inhibitory Synaptic Transmission by Increasing the Content of Norepinephrine in the Locus Coeruleus of Juvenile Rats

Cited by 4 publications

References 37 publications

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder

Locus coeruleus neuronal activity correlates with behavioral response to acute and chronic doses of methylphenidate (Ritalin) in adolescent rats

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