Effects of Methylphenidate on the Membrane Potential and Current in Neurons of the Rat Locus Coeruleus

Ishimatsu, Masaru; Kidani, Yuri; Tsuda, Atsushi; Akasu, Takashi

doi:10.1152/jn.00463.2001

Cited by 25 publications

(23 citation statements)

References 36 publications

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“…In other brain regions (e.g., the LC and the superior cervical ganglion neurons) (Jeong and Ikeda, 1998;Ishimatsu et al, 2002), NE-mediated inhibition can be based on the activation of a G-protein inward rectifying K ϩ (GIRK) current. We tested the hypothesis that NE activates a GIRK current in hypocretin cells.…”

Section: Ne-induced Girk Currentmentioning

confidence: 99%

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Liu¹,

Pol²

2005

J. Neurosci.

112

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Hypothalamic hypocretin enhances arousal, similar to the actions of norepinephrine (NE). The physiological actions of NE were examined in hypocretin neurons identified by selective green fluorescent protein expression in transgenic mouse hypothalamic slices using whole-cell recording. NE induced an outward current, inhibited spike frequency, and hyperpolarized hypocretin neurons dose dependently. Similar actions were evoked by the selective ␣2 adrenergic agonist clonidine. The ␣2 antagonist idazoxan increased spike frequency, suggesting tonic NE-mediated inhibition. The NE-induced current was inwardly rectified, and the reversal potential was dependent on external potassium concentration; it was blocked by barium in the bath and by GTP-␥-S in the pipette, suggesting activation of a G-protein inward rectifying K ϩ (GIRK) current. NE and clonidine decreased calcium currents evoked by depolarizing voltage steps. The selective ␣1 adrenergic agonist phenylephrine had no effect on membrane potential but did increase IPSC frequency; miniature IPSC frequency was also increased, in some cells without any effect on amplitude, suggesting a facilitative presynaptic action at ␣1 receptors on GABAergic axons that innervate hypocretin neurons. NE therefore inhibits hypocretin neurons directly through two mechanisms: activation of a GIRK current, depression of calcium currents, and indirectly through increased inhibitory GABA input. Similar to NE, dopamine and epinephrine reduced or blocked spikes and, in the presence of TTX, showed direct hyperpolarizing actions. The action of dopamine was blocked by the D2 receptor antagonist eticlopride, whereas a D1/5 antagonist had no effect. These data suggest that catecholamines evoke strong inhibitory actions on hypocretin neurons and suggest negative feedback from catecholamine cells that may be excited by hypocretin.

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Section: Ne-induced Girk Currentmentioning

confidence: 99%

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Liu¹,

Pol²

2005

J. Neurosci.

112

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“…36). In this context, it is important to note that attention-deficit hyperactivity disorder has been linked to disorders involving lipid metabolism 38 , pesticide exposure 28,29 and changes in ionchannel conductance in rat models 39 . Taken together, this evidence suggests that in mammals, the catalytic activity of NTE is linked to the control of motor activity and that the inhibition of NTE in humans may contribute to some hyperactivity disorders.…”

Section: Figmentioning

confidence: 99%

Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity

et al. 2003

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“…These are then used for an uptake assay with a radioactive marked substance or for a ligand binding assays using a radioligand and a nonradioactive competitor. 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).…”

Section: Drug Binding and Transport Inhibitionmentioning

confidence: 92%

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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Effects of Methylphenidate on the Membrane Potential and Current in Neurons of the Rat Locus Coeruleus

Cited by 25 publications

References 36 publications

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity

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

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