In vivo electrophysiological effects of methylphenidate in the prefrontal cortex: Involvement of dopamine D1 and alpha 2 adrenergic receptors
Abstract
Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychiatric disorder in children. Psychostimulants such as methylphenidate (MPH) are used as first line treatment. The prefrontal cortex (PFC) has a proven role in the expression of ADHD. Previous studies from our laboratory have demonstrated that MPH activates the firing activity of medial PFC neurones in anaesthetised rats. The aim of the present study was to determine the respective contribution and location of the different types of catecholamine receptors in mediating these excitatory effects and to compare these effects with those induced by other selective dopamine or noradrenaline uptake blockers. Single unit activity of presumed pyramidal PFC neurones was recorded in rats anaesthetised with urethane. The activation of firing elicited by an iv administration of MPH (1 or 3mg/kg) was partially reduced or prevented by the selective D1 receptor antagonist SCH 23390 administered systemically (0.5mg/kg, iv), or locally by passive diffusion through the recording electrode. On the other hand, administration of the alpha 2 receptor antagonist yohimbine (1mg/kg, iv) significantly potentiated the excitatory effect of MPH and activated PFC neurones previously treated with a low inactive dose of MPH (0.3mg/kg, iv). Local administration of MPH (1mM through the recording electrode) significantly increased the firing of PFC neurones in a D1 receptor-dependent manner. In addition, the response of PFC neuro…
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MPH exerts excitatory actions on PFC neurons by activating ADRA2.
“Moreover, it has been shown that MPH exerts excitatory actions on PFC neurons by activating ADRA2 [175, 176].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [175]
In PFC neurons, MPH indirectly activates the postsynaptic DRD1 and DRD5 that uptake DA and transmit the signal in postsynaptic neurons.
“In PFC neurons, MPH indirectly activates the postsynaptic DRD1 and DRD5 [142] that uptake DA and transmit the signal in postsynaptic neurons [175].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [175]
Cites
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Methylphenidate Increases Cortical Excitability via Activation of Alpha-2 Noradrenergic Receptors
Andrews, G. D., & Lavin, A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300818 · Cited by 101 · see citing works
Locomotor hyperactivity induced by blockade of prefrontal cortical α2-adrenoceptors in monkeys
Ma, C.-L., Arnsten, A. F. T., & Li, B.-M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.004 · Cited by 96 · see citing works
Methylphenidate facilitates learning-induced amygdala plasticity
Tye, K. M., Tye, L. D., Cone, J. J., Hekkelman, E. F., Janak, P. H., & Bonci, A. (2010) · Nature Neuroscience · doi:10.1038/nn.2506 · Cited by 89 · see citing works
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Gronier, B., Savignac, H. M., Di Miceli, M., Idriss, S. M., Tzortzis, G., Anthony, D., & Burnet, P. W. J. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.11.001 · Cited by 91 · see citing works
Self-citationQuintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“The DRD1, DRD5, ADRA2A, ADRA2B and ADRA2C are activated downstream by LDX [155, 158, 159].”
BackgroundInfluential
- Authors
- Gronier, B.
- Affiliations
- De Montfort University (GB)
- Corresponding author
- Gronier, Benjamin
- ORCID
- Gronier, Benjamin
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 21
- Issue
- 2
- Pages
- 192-204
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1978723139
- Cited by
- 44
- References
- 5
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 7 · 2012: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- DMU Open Research Archive (De Montfort University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- methylphenidate, prefrontal cortex, dopamine D1 receptor, alpha2-adrenoceptors, attention deficit hyperactivity disorder, single-unit activity, neuronal firing rate, yohimbine, SCH 23390, GBR 12909, desipramine, dopamine reuptake inhibitors, norepinephrine, psychostimulants, local drug administration
- MeSH terms
- Adrenergic beta-Antagonists, Animals, Dopamine, Dose-Response Relationship, Drug, Male, Methylphenidate, Yohimbine, Rats, Sprague-Dawley, Prefrontal Cortex, Receptors, Dopamine D1, Receptors, Dopamine D2, Receptors, Adrenergic, alpha-2, Dopamine Uptake Inhibitors, Rats, Electrophysiological Phenomena, Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-2 Receptor Antagonists
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