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

Andrews, Glenn D; Lavin, Antonieta

doi:10.1038/sj.npp.1300818

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

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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Methylphenidate directly interacts with adrenergic receptors, and through α2 adrenergic receptor activation it stimulates cortical excitability.
“Multiple studies have demonstrated that MPH also directly interacts with adrenergic receptors (109, 115, 119, 120). Through activation of α2 adrenergic receptors, MPH has been demonstrated to stimulate cortical excitability (109).”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [109]
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 [176]

Regional and cellular fractionation of working memory
Goldman‐Rakic, P. S. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13473 · Cited by 810 · see citing works
Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration
Solanto, M. V. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00175-7 · Cited by 677 · see citing works
Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain
Mehta, M. A., Owen, A. M., Sahakian, B. J., Mavaddat, N., Pickard, J. D., & Robbins, T. W. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-06-j0004.2000 · Cited by 608 · cited 1× · see citing works
“Moreover, MPH improves WM performance in healthy subjects (Elliot et al, 1997; Mehta et al, 2000) and several studies have shown that MPH increases overall speed and accuracy of attentional process in normal adults (Strauss et al, 1984; Solanto, 1998).”
Background
Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys
Arnsten, A. F. T., Cai, J. X., Murphy, B. L., & Goldman-Rakic, P. S. (1994) · Psychopharmacology · doi:10.1007/bf02245056 · Cited by 566 · see citing works
Multiple Ionic Conductances of the Human Dopamine Transporter: The Actions of Dopamine and Psychostimulants
Sonders, M. S., Zhu, S.-J., Zahniser, N. R., Kavanaugh, M. P., & Amara, S. G. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-03-00960.1997 · Cited by 446 · see citing works
Biochemical and Histochemical Studies on the Effects of Imipramine‐like Drugs and (+)‐Amphetamine on Central and Peripheral Catecholamine Neurons
Carlsson, A., Fuxé, K., Hamberger, B., & Lindqvist, M. (1966) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1966.tb03334.x · Cited by 412 · see citing works
Effects of methylphenidate on spatial working memory and planning in healthy young adults
Elliott, R., Sahakian, B. J., Matthews, K., Bannerjea, A., Rimmer, J., & Robbins, T. W. (1997) · Psychopharmacology · doi:10.1007/s002130050284 · Cited by 389 · see citing works
Dopamine D1 receptor actions in layers V-VI rat prefrontal cortex neurons in vitro: modulation of dendritic-somatic signal integration
Yang, C., & Seamans, J. K. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-05-01922.1996 · Cited by 369 · see citing works
Brainstem innervation of prefrontal and anterior cingulate cortex in the rhesus monkey revealed by retrograde transport of HRP
Porrino, L. J., & Goldman, P. S. (1982) · The Journal of Comparative Neurology · doi:10.1002/cne.902050107 · Cited by 363 · see citing works
Amphetamine and Related Compounds
Cole, M. (2003) · Analytical techniques in the sciences · doi:10.1002/0470868007.ch2 · Cited by 326 · see citing works
The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is widespread but regionally specific
Lewis, D., Campbell, M., Foote, S., Goldstein, M., & Morrison, J. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-01-00279.1987 · Cited by 325 · see citing works
A COMPARISON OF THE CAPACITIES OF ISOMERS OF AMPHETAMINE, DEOXYPIPRADROL AND METHYLPHENIDATE TO INHIBIT THE UPTAKE OF TRITIATED CATECHOLAMINES INTO RAT CEREBRAL CORTEX SLICES, SYNAPTOSOMAL PREPARATIONS OF RAT CEREBRAL CORTEX, HYPOTHALAMUS AND STRIATUM AND INTO ADRENERGIC NERVES OF RABBIT AORTA
Ferris, R. M., Tang, F. L. M., & Maxwell, R. A. (1972) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29222-9 · Cited by 303 · see citing works
Ventral Tegmental Area Afferents to the Prefrontal Cortex Maintain Membrane Potential 'Up' States in Pyramidal Neurons via D1 Dopamine Receptors
Lewis, B. L. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.12.1168 · Cited by 287 · see citing works
Characterization of α2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones
Williams, J., Henderson, G., & North, R. A. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90166-6 · Cited by 262 · see citing works
Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys
Arnsten, A. F. T., Cai, J., Steere, J. C., & Goldman-Rakic, P. S. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03429.1995 · Cited by 254 · see citing works
Anti-hyperactivity medication: methylphenidate and amphetamine
Seeman, P., & Madras, B. K. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000421 · Cited by 252 · see citing works
A Neurocomputational Theory of the Dopaminergic Modulation of Working Memory Functions
Durstewitz, D., Kelc, M., & Güntürkün, O. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02807.1999 · Cited by 226 · see citing works
Perikaryal and synaptic localization ofα2A-adrenergic receptor-like immunoreactivity
Aoki, C. J., Go, C.-G., Venkatesan, C., & Kurose, H. (1994) · Brain Research · doi:10.1016/0006-8993(94)91782-5 · Cited by 221 · see citing works
The dopamine mesocorticolimbic pathway is affected by deficiency in n−3 polyunsaturated fatty acids
Zimmer, L., Vancassel, S., Cantagrel, S., Breton, P., Delamanche, S., Guilloteau, D., Durand, G., & Chalon, S. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.4.662 · Cited by 218 · see citing works
Noradrenaline‐mediated synaptic inhibition in rat locus coeruleus neurones.
Egan, T. M., Henderson, G., North, R. A., & Williams, J. T. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014990 · Cited by 199 · see citing works
Effects of dopamine antagonists on neuronal activity related to a delayed response task in monkey prefrontal cortex
Sawaguchi, T., Matsumura, M., & Kubota, K. (1990) · Journal of Neurophysiology · doi:10.1152/jn.1990.63.6.1401 · Cited by 199 · see citing works
Region‐specific distribution of catecholamine afferents in primate cerebral cortex: A fluorescence histochemical analysis
Levitt, P., RAKIC, P. T., & Goldman‐Rakic, P. S. (1984) · The Journal of Comparative Neurology · doi:10.1002/cne.902270105 · Cited by 191 · see citing works
Prefrontal neurons in networks of executive memory
Fuster, J. M. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(99)00258-0 · Cited by 166 · see citing works
Biochemistry of Somatodendritic Dopamine Release in Substantia Nigra: An In Vivo Comparison with Striatal Dopamine Release
Heeringa, M. J., & Abercrombie, E. D. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65010192.x · Cited by 144 · see citing works
Cellular and subcellular sites for noradrenergic action in the monkey dorsolateral prefrontal cortex as revealed by the immunocytochemical localization of noradrenergic receptors and axons
Aoki, C. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.3.269 · Cited by 138 · see citing works
Noradrenergic innervation of monkey prefrontal cortex: A dopamine‐β‐hydroxylase immunohistochemical study
Lewis, D. A., & Morrison, J. H. (1989) · The Journal of Comparative Neurology · doi:10.1002/cne.902820302 · Cited by 131 · see citing works
Opiate- and alpha 2-adrenoceptor-induced hyperpolarizations of locus ceruleus neurons in brain slices: reversal by cyclic adenosine 3':5'- monophosphate analogues
Andrade, R., & Aghajanian, G. K. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-09-02359.1985 · Cited by 130 · see citing works
Ultrastructural localization of the norepinephrine transporter in superficial and deep layers of the rat prelimbic prefrontal cortex and its spatial relationship to probable dopamine terminals
Miner, L. H., Schroeter, S., Blakely, R., & Sesack, S. R. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10898 · Cited by 112 · see citing works
Effects of methylphenidate on young adults' performance and event-related potentials in a vigilance and a paired-associates learning test
Strauss, J., Lewis, J. L., Klorman, R., Peloquin, L., Perlmutter, R. A., & Salzman, L. F. (1984) · Psychophysiology · doi:10.1111/j.1469-8986.1984.tb00247.x · Cited by 90 · see citing works
Stimulation of D1-type dopamine receptors enhances excitability in prefrontal cortical pyramidal neurons in a state-dependent manner
Lavı́n, A., & Grace, A. A. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00096-3 · Cited by 87 · see citing works
Treatment effects of oral and transdermal clonidine in relation to methylphenidate: an open pilot study in ADD-H.
Rd, H. (1987) · PubMed · Cited by 85 · see citing works
Possible change in noradrenergic receptor sensitivity following methylphenidate treatment: Growth hormone and MHPG response to clonidine challenge in children with attention deficit disorder and hyperactivity
Hunt, R. D., Cohen, D. J., Anderson, G. M., & Clark, L. R. (1984) · Life Sciences · doi:10.1016/0024-3205(84)90415-6 · Cited by 60 · see citing works
STEREOSELECTIVITY OF CATECHOLAMINE UPTAKE BY BRAIN SYNAPTOSOMES: STUDIES WITH EPHEDRINE, METHYLPHENIDATE AND PHENYL-2-PIPERIDYL CARBINOL
Hendley, E. D., Snyder, S. H., Fauley, J. J., & LaPidus, J. B. (1972) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29320-x · Cited by 37 · see citing works
Antagonism by methylphenidate of the stereotyped behaviour produced by (+)-amphetamine in reserpinized rats
Ross, S. B. (1978) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1978.tb13218.x · Cited by 29 · see citing works
Electrophysiological effects of methylphenidate on the coeruleo-cortical noradrenergic system in the rat
Lacroix, D., & Ferron, A. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90658-9 · Cited by 23 · see citing works
Abnormal retinotopic organization of the dorsal lateral geniculate nucleus of the tyrosinase-negative albino cat
SCHMOLESKY, M. T., Wang, Y., Creel, D. J., & Leventhal, A. G. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001113)427:2 · Cited by 13 · see citing works

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Sorted by citations

Candidate gene studies of ADHD: a meta-analytic review
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009) · Human Genetics · doi:10.1007/s00439-009-0694-x · Cited by 1,020 · see citing works
Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation
Samuels, E., & Szabadi, E. (2008) · Current Neuropharmacology · doi:10.2174/157015908785777229 · Cited by 766 · see citing works
The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities
Faraone, S. V. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.02.001 · Cited by 631 · see citing works
Functional neuroanatomy of the central noradrenergic system
Szabadi, E. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113490326 · Cited by 337 · see citing works
Effects of Methylphenidate on the Catecholaminergic System in Attention-Deficit/Hyperactivity Disorder
Wilens, T. E. (2008) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318173312f · Cited by 269 · see citing works
Adrenoceptors in brain: Cellular gene expression and effects on astrocytic metabolism and [Ca2+]i
Hertz, L., Lovatt, D., Goldman, S. A., & Nedergaard, M. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.03.019 · Cited by 234 · see citing works
Alcohol and the prefrontal cortex
Abernathy, K., Chandler, L. J., & Woodward, J. J. (2010) · International Review of Neurobiology · doi:10.1016/s0074-7742(10)91009-x · Cited by 196 · see citing works
Pharmacology of stimulants prohibited by the World Anti‐Doping Agency (WADA)
Docherty, J. R. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.124 · Cited by 143 · see citing works
Genetics of attention-deficit hyperactivity disorder (ADHD).
Sharp, S., McQuillin, A., & Gurling, H. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.011 · Cited by 131 · see citing works
α2‐Noradrenergic receptors activation enhances excitability and synaptic integration in rat prefrontal cortex pyramidal neurons via inhibition of HCN currents
Carr, D. B., Andrews, G. D., Glen, W. B., & Lavı́n, A. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.141671 · Cited by 119 · see citing works
Self-citation
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Polanczyk, G. V., Zeni, C., Genro, J. P., Guimarães, A. P., Roman, T., Hutz, M. H., & Rohde, L. A. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.2.218 · Cited by 115 · see citing works
Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD
Myer, N. M., Boland, J. R., & Faraone, S. V. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.234 · Cited by 91 · see citing works
Progress and Promise of Attention-Deficit Hyperactivity Disorder Pharmacogenetics
Froehlich, T. E., McGough, J., & Stein, M. (2010) · CNS Drugs · doi:10.2165/11530290-000000000-00000 · Cited by 91 · see citing works
Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review
Jaeschke, R. R., Sujkowska, E., & Sowa-Kućma, M. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05946-0 · Cited by 90 · see citing works
Association between dietary behaviors and attention-deficit/hyperactivity disorder and learning disabilities in school-aged children
Park, S., Cho, S.-C., Hong, Y., Oh, S., Kim, J.-W., Shin, M., Kim, B., Yoo, H., Cho, I.-H., & Bhang, S. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2012.02.012 · Cited by 78 · see citing works
Dopamine D1/5 Receptor-Mediated Long-Term Potentiation of Intrinsic Excitability in Rat Prefrontal Cortical Neurons: Ca2+-Dependent Intracellular Signaling
Chen, L., Bohanick, J. D., Nishihara, M., Seamans, J. K., & Yang, C. R. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00317.2006 · Cited by 79 · see citing works
Update on 3-iodothyronamine and its neurological and metabolic actions
Zucchi, R., Accorroni, A., & Chiellini, G. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00402 · Cited by 76 · see citing works
Layer- and area-specific actions of norepinephrine on cortical synaptic transmission
Salgado, H., Treviño, M., & Atzori, M. (2016) · Brain Research · doi:10.1016/j.brainres.2016.01.033 · Cited by 71 · see citing works
Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review
Quintero, 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
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Bisagno, V., González, B., & Urbano, F. J. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.01.013 · Cited by 59 · see citing works
Event-based control of autonomic and emotional states by the anterior cingulate cortex
Seamans, J. K., & Floresco, S. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.026 · Cited by 58 · see citing works
The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults
Farr, O. M., Zhang, S., Hu, S., Matuskey, D., Abdelghany, O., Malison, R. T., & Li, C.-S. R. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000674 · Cited by 57 · see citing works
Distinct Age-Dependent Effects of Methylphenidate on Developing and Adult Prefrontal Neurons
Urban, K. R., Waterhouse, B. D., & Gao, W. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.018 · Cited by 57 · see citing works
Guanfacine Extended Release: A New Pharmacological Treatment Option in Europe
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Performance Enhancing, Non-Prescription Use of Ritalin
Svetlov, S. I., Kobeissy, F. H., & Gold, M. S. (2007) · Journal of Addictive Diseases · doi:10.1300/j069v26n04_01 · Cited by 55 · see citing works
From Clinical Application to Cognitive Enhancement: The Example of Methylphenidate
Busardò, F., Kyriakou, C., Cipolloni, L., Zaami, S., & Frati, P. (2016) · Current Neuropharmacology · doi:10.2174/1570159x13666150407225902 · Cited by 52 · see citing works
ADHD pharmacogenetics across the life cycle: New findings and perspectives
Bruxel, E. M., Akutagava-Martins, G. C., Salatino-Oliveira, A., Contini, V., Kieling, C., Hutz, M., & Rohde, L. (2014) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32240 · Cited by 44 · see citing works
The effect of methylphenidate on auditory information processing in healthy volunteers: a combined EEG/MEG study
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Dopaminergic modulation of brain systems subserving decision making under uncertainty: A study with fMRI and methylphenidate challenge
Schlösser, R. G. M., Nenadić, I., Wagner, G., Zysset, S., Koch, K., & Sauer, H. (2009) · Synapse · doi:10.1002/syn.20621 · Cited by 44 · see citing works
Noradrenergic alterations in Parkinson’s disease: a combined 11C-yohimbine PET/neuromelanin MRI study
Laurencin, C., Lancelot, S., Brosse, S., Mérida, I., Redouté, J., Greusard, E., Lamberet, L., Liotier, V., Bars, D. L., Costes, N., et al. (2023) · Brain · doi:10.1093/brain/awad338 · Cited by 43 · see citing works
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Cathel, A. M., Reyes, B. A. S., Wang, Q., Palma, J. D., Mackie, K., Bockstaele, E. J. V., & Kirby, L. G. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12690 · Cited by 43 · see citing works
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Grzelka, K., Kurowski, P. N., Gawlak, M., & Szulczyk, P. J. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00341 · Cited by 38 · see citing works
In vivo electrophysiological effects of methylphenidate in the prefrontal cortex: Involvement of dopamine D1 and alpha 2 adrenergic receptors
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YY162 prevents ADHD-like behavioral side effects and cytotoxicity induced by Aroclor1254 via interactive signaling between antioxidant potential, BDNF/TrkB, DAT and NET
Nam, Y., Shin, E., Shin, S. W., Lim, Y. K., Jung, J. H., Lee, J. H., Ha, J. R., Chae, J. S., Ko, S. K., Jeong, J. H., et al. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.12.046 · Cited by 35 · see citing works
PharmGKB summary
Stevens, T., Sangkuhl, K., Brown, J. T., Altman, R. B., & Klein, T. E. (2019) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000376 · Cited by 34 · see citing works
Atomoxetine improves sleepiness and global severity of illness but not the respiratory disturbance index in mild to moderate obstructive sleep apnea with sleepiness
Sangal, R. B., Sangal, J. M., & Thorp, K. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2007.07.013 · Cited by 34 · see citing works
Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure
Reyes, B. A. S., Szot, P., Sikkema, C. L., Cathel, A. M., Kirby, L. G., & Bockstaele, E. J. V. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.05.016 · Cited by 34 · see citing works
Pharmacotherapy for Attention-Deficit/Hyperactivity Disorder: From Cells to Circuits
Minzenberg, M. J. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0128-7 · Cited by 41 · see citing works
Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children
Yang, L., Qian, Q., Liu, L., Li, H.-M., Faraone, S., & Wang, Y.-F. (2013) · Journal of neural transmission · doi:10.1007/s00702-012-0955-z · Cited by 35 · see citing works
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Faraone, S. V., & Radonjić, N. V. (2023) · Springer eBooks · doi:10.1007/978-3-030-42825-9_33-1 · Cited by 31 · see citing works
Effect of antidepressant drugs on the vmPFC-limbic circuitry
Chang, C. H., Chen, M. C., & Lu, J. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.01.010 · Cited by 30 · see citing works
Clinical and neurobiological factors in the management of treatment refractory attention-deficit hyperactivity disorder
Shim, S.-H., Yoon, H.-J., Bak, J., Hahn, S., & Kim, Y. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.04.007 · Cited by 29 · see citing works
Noradrenergic fiber sprouting and altered transduction in neuropathic prefrontal cortex
Matos, S. C., Zamfir, M., Longo, G., Ribeiro‐da‐Silva, A., & Séguéla, P. (2017) · Brain Structure and Function · doi:10.1007/s00429-017-1543-7 · Cited by 28 · see citing works
Possible association of norepinephrine transporter -3081(A/T) polymorphism with methylphenidate response in attention deficit hyperactivity disorder
Kim, B.-N., Kim, J.-W., Hong, S.-B., Cho, S.-C., Shin, M., & Yoo, H. (2010) · Behavioral and Brain Functions · doi:10.1186/1744-9081-6-57 · Cited by 28 · see citing works
Effects of Methylphenidate on Cognitive Function in Adults with Traumatic Brain Injury: A Meta-Analysis
Chien, Y.-J., Chien, Y.-C., Liu, C.-T., Wu, H.-C., Chang, C.-Y., & Wu, M.-Y. (2019) · Brain Science · doi:10.3390/brainsci9110291 · Cited by 25 · see citing works
REM sleep loss–induced elevated noradrenaline could predispose an individual to psychosomatic disorders: a review focused on proposal for prediction, prevention, and personalized treatment
Mehta, R., Giri, S., & Mallick, B. N. (2020) · The EPMA Journal · doi:10.1007/s13167-020-00222-1 · Cited by 24 · see citing works
Norepinephrine Genes Predict Response Time Variability and Methylphenidate-Induced Changes in Neuropsychological Function in Attention Deficit Hyperactivity Disorder
Kim, B.-N., Kim, J.-W., Cummins, T. D. R., Bellgrove, M. A., Hawi, Z., Hong, S.-B., Yang, Y.-H., Kim, H.-J., Shin, M., Cho, S.-C., et al. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31828f9fc3 · Cited by 24 · see citing works
Genetic Influence on Efficacy of Pharmacotherapy for Pediatric Attention-Deficit/Hyperactivity Disorder: Overview and Current Status of Research
Elsayed, N. A., Yamamoto, K. M., & Froehlich, T. E. (2020) · CNS Drugs · doi:10.1007/s40263-020-00702-y · Cited by 23 · see citing works
Mapping the central effects of methylphenidate in the rat using pharmacological MRI BOLD contrast
Easton, N., Marshall, F. H., Marsden, C. A., & Fone, K. C. F. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.018 · Cited by 22 · see citing works
Dysregulation of gene induction in corticostriatal circuits after repeated methylphenidate treatment in adolescent rats: differential effects on zif 268 and homer 1a
Cotterly, L. M., Beverley, J. A., Yano, M., & Steiner, H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05570.x · Cited by 22 · see citing works
Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis
Yuan, D., Zhang, M., Huang, Y., Wang, X., Jiao, J., & Huang, Y. (2021) · Medicine · doi:10.1097/md.0000000000027858 · Cited by 21 · see citing works
Stress Response, Brain Noradrenergic System and Cognition
Winklewski, P. J., Radkowski, M., Wszędybył-Winklewska, M., & Demkow, U. A. (2017) · Advances in experimental medicine and biology · doi:10.1007/5584_2016_204 · Cited by 21 · see citing works
Effects of Methylphenidate on the Hyperemotional Behavior in Olfactory Bulbectomized Mice by Using the Hole-Board Test
Kamei, J., Hirose, N., Oka, T., Miyata, S., Saitoh, A., & Yamada, M. (2007) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fp0061021 · Cited by 20 · see citing works
Norepinephrine transporter −3081(A/T) and alpha-2A-adrenergic receptor MspI polymorphisms are associated with cardiovascular side effects of OROS-methylphenidate treatment
Cho, S.-C., Kim, B.-N., Cummins, T. D. R., Kim, J.-W., & Bellgrove, M. A. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111405356 · Cited by 19 · see citing works
Activation of 5‐ HT receptors inhibits GABA ergic transmission by pre‐and post‐synaptic mechanisms in layer II/III of the juvenile rat auditory cortex
García‐Oscos, F., Torres‐Ramírez, O., Dinh, L., Galindo‐Charles, L., Padilla, E. A. P., Pineda, J. C., Atzori, M., & Salgado, H. (2014) · Synapse · doi:10.1002/syn.21794 · Cited by 16 · see citing works
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Gronier, B., James, A., Liauzun, C., & Zetterström, T. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881109359100 · Cited by 17 · see citing works
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Kaneko, F., Kawahara, Y., Kishikawa, Y., Hanada, Y., Yamada, M., Kakuma, T., Kawahara, H., & Nishi, A. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw026 · Cited by 18 · see citing works
Lack of association between response of OROS-methylphenidate and norepinephrine transporter (SLC6A2) polymorphism in Korean ADHD
Lee, S. H., Kim, S. W., Lee, M. G., Yook, K.-H., Greenhill, L. L., Frandin, K. N., & Hong, H. J. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2010.08.033 · Cited by 17 · see citing works
A candidate gene investigation of methylphenidate response in adult attention-deficit/hyperactivity disorder patients: results from a naturalistic study
Hegvik, T., Jacobsen, K. K., Fredriksen, M., Zayats, T., & Haavik, J. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1540-7 · Cited by 17 · see citing works
Biological Predictors of Treatment Response in Adult Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review
Capuzzi, E., Caldiroli, A., Auxilia, A. M., Borgonovo, R., Capellazzi, M., Clerici, M., & Buoli, M. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12101742 · Cited by 12 · see citing works
Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion
Reyes, B. A. S., Carvalho, A. F., Szot, P., Kalamarides, D. J., Wang, Q., Kirby, L. G., & Bockstaele, E. J. V. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.03.010 · Cited by 12 · see citing works
Preventative treatment in an animal model of ADHD: Behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats
Lukkes, J. L., Freund, N., Thompson, B. S., Meda, S., & Andersen, S. L. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.06.003 · Cited by 11 · see citing works
The anterior cingulate cortex and event-based modulation of autonomic states
Seamans, J. K. (2021) · International review of neurobiology · doi:10.1016/bs.irn.2020.11.006 · Cited by 10 · see citing works
Sex differences in μ-opioid regulation of coerulear-cortical transmission
Guajardo, H. M., & Valentino, R. J. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135651 · Cited by 10 · see citing works
Single exposure of dopamine D1 antagonist prevents and D2 antagonist attenuates methylphenidate effect
Dafny, N., Claussen, C. M., & Witte, L. J. (2015) · Journal of Experimental Pharmacology · doi:10.2147/jep.s75300 · Cited by 9 · see citing works
In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder
Grünblatt, E., Bartl, J., Marinova, Z., & Walitza, S. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-012-0869-9 · Cited by 9 · see citing works
Bases genéticas del trastorno por déficit de atención/hiperactividad
Sánchez-Mora, C., Ribasés, M., Mulas, F., Soutullo, C., Sans, A., Pàmias, M., Casas, M., & Ramos-Quiroga, J. (2012) · Revista de Neurología · doi:10.33588/rn.5510.2012344 · Cited by 10 · see citing works
Differential Pharmacological Regulation of Sensorimotor Gating Deficit in CB1 Knockout Mice and Associated Neurochemical and Histological Alterations
Ortega-Álvaro, A., Navarrete, F., Aracil-Fernández, A., Navarro, D., Berbel, P. J., & Manzanares, J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.113 · Cited by 8 · see citing works
A Dopamine D1 Agonist Versus Methylphenidate in Modulating Prefrontal Cortical Working Memory
Yang, Y., Lewis, M. M., Kong, L., & Mailman, R. B. (2022) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.122.001215 · Cited by 7 · see citing works
An overview of the efficacy and safety of brexpiprazole for the treatment of schizophrenia in adolescents
Crump, C., Abuelazm, H., Ibrahim, K., Shah, S. R., & El‐Mallakh, R. S. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2367695 · Cited by 7 · see citing works
CRISPR/Cas9‐induced nos2b mutant zebrafish display behavioral abnormalities
Gao, L., Penglee, R., Huang, Y., Yi, X., Wang, X., Liu, L., Gong, X., & Bao, B. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12716 · Cited by 6 · see citing works
Acute administration of methylphenidate alters the prefrontal cortex neuronal activity in a dose–response characteristic
Dafny, N., & Claussen, C. M. (2014) · Journal of Experimental Pharmacology · doi:10.2147/jep.s53497 · Cited by 6 · see citing works
Probable Methylphenidate-Related Reversible “Visual Snow” in a Child With ADHD
Naguy, A., Naguy, C., & Singh, A. (2022) · Clinical Neuropharmacology · doi:10.1097/wnf.0000000000000512 · Cited by 6 · see citing works
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Yaoita, F., Tsuchiya, M., Arai, Y., Tadano, T., & Tan–No, K. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.12.002 · Cited by 6 · see citing works
Involvement of the Hippocampal Alpha2A-Adrenoceptors in Anxiety-Related Behaviors Elicited by Intermittent REM Sleep Deprivation-Induced Stress in Mice
Yaoita, F., Namura, K., Shibata, K., Sugawara, S., Tsuchiya, M., Tadano, T., & Tan–No, K. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b20-00255 · Cited by 6 · see citing works
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Navarra, R. L., & Waterhouse, B. D. (2018) · Brain Research · doi:10.1016/j.brainres.2018.06.027 · Cited by 5 · see citing works
Treating Attention Deficits and Impulse Control
Timmers, D. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-396988-0.00006-4 · Cited by 5 · see citing works
Catecholaminergic Modulation of Semantic Processing in Sentence Comprehension
Tan, Y., & Peter Hagoort, A. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa204 · Cited by 4 · see citing works
Attention Deficit Hyperactivity Disorder
Marco, P., Maddalena, M., Bertella, S., Gatti, E., & Nobile, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00164-x · Cited by 4 · see citing works
Aloud real- time reading of intensive care unit diaries: A feasibility study
Johnson, K. R., Temeyer, J. P., Schulte, P. J., Nydahl, P., Philbrick, K. L., & Karnatovskaia, L. V. (2023) · Intensive and Critical Care Nursing · doi:10.1016/j.iccn.2023.103400 · Cited by 4 · see citing works
Disciplined sleep for healthy living: Role of noradrenaline
Mehta, R., Singh, A., & Mallick, B. N. (2017) · World Journal of Neurology · doi:10.5316/wjn.v7.i1.6 · Cited by 4 · see citing works
The Treatment of Adult ADHD: Complexity at Hand
Pallanti, S., & Salerno, L. (2020) · Springer eBooks · doi:10.1007/978-3-030-39051-8_19 · Cited by 3 · see citing works
Methylphenidate modulates motor cortical dynamics and behaviorPreprint
Verhein, J. R., Vyas, S., & Shenoy, K. V. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.15.562405 · Cited by 3 · see citing works
Methylphenidate (MPH) promotes visual cortical activation in healthy adults in a cued visuomotor task
Hodzhev, Y., Yordanova, J., Diruf, M., Kratz, O., Moll, G. H., Kolev, V., & Heinrich, H. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-012-0799-6 · Cited by 3 · see citing works
Regulation of Cortical Functions by the Central Noradrenergic System: Emerging Properties from an Old Friend
Atzori, M., Salgado, H., & Tseng, K.-Y. (2007) · Springer eBooks · doi:10.1007/978-0-387-72256-6_13 · Cited by 2 · see citing works
Neurofibromatosis Type I Learning Disabilities
Shilyansky, C., Wiltgen, B. J., & Silva, A. J. (2008) · Elsevier eBooks · doi:10.1016/b978-012370509-9.00019-x · Cited by 2 · see citing works
Pharmacogenomics of Attention-Deficit/Hyperactivity Disorder
Froehlich, T. E., & Stein, M. A. (2010) · Advances in biological psychiatry · doi:10.1159/000317300 · Cited by 1 · see citing works
METHYLPHENIDATE AND ATOMOXETINE TREATMENT DURING ADOLESCENCE IN THE SPONTANEOUSLY HYPERTENSIVE RAT: MECHANISMS UNDERLYING HIGH COCAINE ABUSE LIABILITY IN ATTENTION DEFICIT/HYPERACTIVITY DISORDER
Somkuwar, S. S. (2013) · UKnowledge (University of Kentucky)
Metilfenidato causa alterações neuroquímicas e comportamentais em ratos
Scherer, E. B. D. S. (2010) · Americanae (AECID Library)
AD(H)S, Körperkontaktstörung und Körperbezogene Interaktionstherapie (KIT)
Smikalla, W.-D. (2014) · Springer eBooks · doi:10.1007/978-3-642-41118-2_17
and Arc gene expression measurements Age-dependent effects of methylphenidate in the prefrontal cortex: evidence from electrophysiological
Gronier, B., Aston, J., Liauzun, C., & Zetterström, T. (2011)
Stosowanie środków psychostymulujących w leczeniu wspomagającym i paliatywnym pacjentów z chorobą nowotworową
Kaminski, M., & Sjøgren, P. (2008) · Via Medica Journals
Dopamine D4 receptor deficiency alters behavioral responsiveness of mice to methylphenidate
Keck, T. M. (2009) · doi:10.13140/2.1.4692.8008
Review of Select Sleep Medicine Pharmacology: Treatments of Hypersomnias and Parasomnia
Johnson, K., Mansukhani, M. P., & Kolla, B. P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00163-8
Neurobiology and Genetics of Pair Bonding: A New HypothesisPreprint
Gadda, N. S. (2022) · doi:10.31219/osf.io/cvz58
Neurobiology of Attention Deficit Hyperactivity Disorder
Faraone, S. V., & Radonjić, N. V. (2024) · Springer eBooks · doi:10.1007/978-3-030-51366-5_33 · Cited by 1 · see citing works
Dynamic Routing on a Static Structure: Noradrenergic Gating of Cortical Wave PropagationPreprint
Maran, R., Shine, J. M., Fulcher, B., & Müller, E. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.10.705210

In vivo electrophysiological effects of methylphenidate in the prefrontal cortex: Involvement of dopamine D1 and alpha 2 adrenergic receptors
Gronier, B. (2011) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2010.11.002 · Cited by 44 · see citing works
Methylphenidate improves prefrontal cortical cognitive function through α2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder
Arnsten, A. F., & Dudley, A. G. (2005) · Behavioral and Brain Functions · doi:10.1186/1744-9081-1-2 · Cited by 363 · see citing works
Methylphenidate Enhances NMDA-Receptor Response in Medial Prefrontal Cortex via Sigma-1 Receptor: A Novel Mechanism for Methylphenidate Action
(2016)
Methylphenidate and Atomoxetine Enhance Prefrontal Function Through α2-Adrenergic and Dopamine D1 Receptors
Gamo, N. J., Wang, M., & Arnsten, A. F. T. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.06.015 · Cited by 232 · see citing works
Methylphenidate significantly alters the functional coupling between the prefrontal cortex and dopamine neurons in the ventral tegmental area
Peña, I. D., Shen, G., & Shi, W. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.01.015 · Cited by 13 · see citing works

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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