Cited by 101Attention Deficit Hyperactivity DisorderNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Methylphenidate Increases Cortical Excitability via Activation of Alpha-2 Noradrenergic Receptors

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Andrews, Glenn D, Lavin, Antonieta·2006·Neuropsychopharmacology

DOI 10.1038/sj.npp.1300818PMC PMC5509071

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Abstract

Although methylphenidate (MPH), a catecholaminergic reuptake blocker, is prescribed for attention-deficit/hyperactivity disorder, there is a dearth of information regarding the cellular basis of its actions. To address this issue, we used whole-cell patch-clamp recordings to investigate the roles of various catecholamine receptors in MPH-induced changes in cortical neuron excitability. We bath-applied dopamine or noradrenaline receptor antagonists in combination with MPH to pyramidal cells located in deep layers of the infralimbic and prelimbic prefrontal cortices. Application of MPH (10 microM) by itself increased cortical cell excitability in slices obtained from juvenile rats. This MPH-mediated increase in excitability was lost when catecholamines were depleted with reserpine prior to recording, demonstrating the requirement for a presynaptic monoamine component. Antagonist studies further revealed that stimulation of alpha-2 noradrenergic receptors mediates the MPH-induced increase in intrinsic excitability. Dopamine D1 receptors played no observable role in the actions of MPH. We therefore propose that MPH is acting to increase catecholaminergic tone in the PFC, and thereby increases cortical excitability by mediating the disinhibition of pyramidal cells through mechanisms that may include activation of alpha-2 adrenoreceptors located in interneurons.

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Authors: Andrews, G. D., & Lavin, A.
Affiliations: Medical University of South Carolina (US)
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2005-07-06
Volume: 31
Issue: 3
Pages: 594-601
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300818
PMC: PMC5509071
OpenAlex: W2018418849
Cited by: 101
References: 36
Citations by year: 2026: 1 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 8 · 2013: 4 · 2012: 9
FWCI: 2.82
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (14698)
National Institute on Drug Abuse (R01DA014698, R56DA014698, DA 14698)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: methylphenidate, alpha2-adrenoceptors, cortical excitability, prefrontal cortex, pyramidal neurons, catecholamine depletion, reserpine, dopamine D1 receptor, norepinephrine, attention deficit hyperactivity disorder, disinhibition, interneurons
MeSH terms: Adrenergic alpha-Agonists, Adrenergic alpha-Antagonists, Central Nervous System Stimulants, Animals, Catecholamines, Cerebral Cortex, Dopamine, Electrophysiology, Male, Methylphenidate, Nerve Net, Norepinephrine, Prefrontal Cortex, Pyramidal Cells, Receptors, Adrenergic, alpha-2, Dopamine Agonists, Rats, In Vitro Techniques

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Methylphenidate Increases Cortical Excitability via Activation of Alpha-2 Noradrenergic Receptors

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