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Non\u2010invasive brain stimulation techniques can induce plasticity and monitor cortical facilitation and inhibition in humans. In a randomized, placebo\u2010controlled, double\u2010blinded study, we investigated how dopamine and D1\u2010 and D2\u2010like receptors impact transcranial direct current stimulation (tDCS)\u2010induced plasticity concerning glutamatergic and GABAergic mechanisms. Eighteen healthy volunteers received 1\u2009mA anodal (13\u2009min) and cathodal tDCS (9\u2009min) over the left motor cortex combined with the dopaminergic agents l\u2010dopa (general dopamine activation), bromocriptine (D2\u2010like receptor agonist), combined D2 antagonism via sulpiride and general dopaminergic activation via l\u2010dopa to activate D1\u2010like receptors, and placebo medication. Glutamate\u2010related cortical facilitation and GABA\u2010related cortical inhibition were monitored using transcranial magnetic stimulation techniques, including I\u2013O curve, intracortical facilitation (ICF), short\u2010interval intracortical inhibition (SICI), and I\u2010wave facilitation protocols. Our results indicate that anodal tDCS alone enhanced the I\u2013O curve and ICF while decreasing SICI. Conversely, cathodal tDCS decreased the I\u2010O curve and ICF while increasing SICI. General dopamine and D2 receptor activation combined with anodal tDCS decreased the I\u2010O curve and ICF, but enhanced SICI compared to tDCS alone. When paired with cathodal tDCS, general dopamine and D2\u2010like receptor activity enhancement prolonged the cathodal tDCS effect on excitability. After anodal tDCS, D1\u2010like receptor activation increased the I\u2010O curve and ICF while reducing SICI. These effects were abolished with cathodal tDCS. Dopaminergic substances combined with anodal and cathodal tDCS did not have a significant effect on I\u2010wave facilitation. These results suggest that D1\u2010like receptor activation enhanced LTP\u2010like plasticity and abolished LTD\u2010like plasticity via glutamatergic NMDA receptor enhancement, while global dopaminergic and D2\u2010like receptor enhancement weakened LTP\u2010like but strengthened LTD\u2010like plasticity primarily via glutamatergic NMDA receptor activity diminution.<\/jats:p>","DOI":"10.1002\/hbm.70162","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T11:46:50Z","timestamp":1739447210000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Contribution of Glutamatergic and <scp>GABAergic<\/scp> Mechanisms to the Plasticity\u2010Modulating Effects of Dopamine in the Human Motor Cortex"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-8123","authenticated-orcid":false,"given":"Elham","family":"Ghanavati","sequence":"first","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"},{"name":"Department of Psychology Ruhr University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-4677","authenticated-orcid":false,"given":"Mohammad Ali","family":"Salehinejad","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"},{"name":"School of Cognitive Sciences Institute for Research in Fundamental Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie C.","family":"Beaupain","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"},{"name":"Department of Psychology Ruhr University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Melo","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amba","family":"Frese","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"},{"name":"International Graduate School of Neuroscience, Ruhr University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Fang","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Nitsche","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neurosciences Leibniz Research Centre for Working Environment and Human Factors (IfADo)  Dortmund Germany"},{"name":"Bielefeld University, University Hospital OWL, Protestant Hospital of Bethel Foundation University Clinic of Psychiatry Psychotherapy  Bielefeld Germany"},{"name":"German Center for Mental Health (DZPG)  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1","article-title":"Dopaminergic Modulation of Synaptic Plasticity, Its Role in Neuropsychiatric Disorders, and Its Computational Modeling","volume":"10","author":"Asl M. 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