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Two competing theories suggest that 10-Hz rTMS induces N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP), and\/or removal of inhibitory gamma-aminobutyric acid receptors (GABARs). We examined these two proposed mechanisms of action in the human motor cortex in a double-blind, randomized, four-arm crossover study in six healthy subjects. We tested plasticity with motor-evoked potentials (MEPs) and learning with serial reaction time task (SRTT) before and after 10-Hz rTMS in the presence of four drugs separated by 1 week each: placebo, d-cycloserine (DCS 100\u2009mg), DCS 100\u2009mg\u2009+\u2009NMDAR partial antagonist dextromethorphan (DXM 150\u2009mg), and lorazepam (LZP 2.5\u2009mg). NMDAR agonism by DCS enhanced rTMS-induced cortical excitability relative to placebo. This facilitation was specifically blocked by combining DCS with DXM. LZP administration resulted in a significant reduction of MEP amplitudes after rTMS. Results suggest that 10-Hz rTMS-induced plasticity works primarily through NMDAR dependent modulation with LTP-like mechanisms as opposed to GABAergic reduction. Our pilot study is the first to compare NMDAR v. GABAR in rTMS-induced plasticity and found the safety and feasibility of a 4-arm crossover protocol with each drug combined with the full 3000 pulse 10-Hz rTMS protocol. Our results may guide future clinical translation leveraging mechanistic understanding to improve therapeutic efficacy.<\/jats:p>","DOI":"10.1038\/s41398-026-04159-3","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:04:01Z","timestamp":1781665441000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploration of NMDA and GABA receptor-mediated plasticity induced by 10-Hz repetitive transcranial magnetic stimulation"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3157-1555","authenticated-orcid":false,"given":"Jamie","family":"Kweon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-3428","authenticated-orcid":false,"given":"Hakjoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7078-693X","authenticated-orcid":false,"given":"Prem","family":"Ganesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Vigne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-3307","authenticated-orcid":false,"given":"Linda L.","family":"Carpenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-2746","authenticated-orcid":false,"given":"Joshua C.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"4159_CR1","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1016\/j.neurom.2021.09.003","volume":"25","author":"JC Brown","year":"2022","unstructured":"Brown JC, Higgins ES, George MS. 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Dr. Carpenter has received research support (to Butler Hospital) from Neuronetics Inc, Neosync Inc, Nexstim PLC, Affect Neuro Inc, Neurolief, Gray Matters Health and Janssen Pharmaceuticals Inc. No other authors declare relevant funding.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"430"}}