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Dose\/concentration\u2010dependent effects of acute\/chronic administrations of\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine (25\u2013300\u2009\u03bcM and 2\u201325\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) on expression of GluN2 subunits and associated transmission of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamate\/\n                      <jats:sc>d<\/jats:sc>\n                      \u2010serine\/GABA were determined using microdialysis in adult male rats, primary cultured astrocytes (male\/female neonatal rats) and capillary immunoblotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine dose\u2010dependently increased release of astroglial\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamate\/\n                      <jats:sc>d<\/jats:sc>\n                      \u2010serine and neuronal GABA in the thalamus and medial prefrontal cortex (mPFC) (\n                      <jats:sc>d<\/jats:sc>\n                      \u2010serine\u2009&gt;\u2009GABA\u2009&gt;\u2009\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamate), according to intrinsic activities (GluN2C\u2009&gt;\u2009GluN2A [but unaffected GluN2B]). Chronic\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine dose\u2010dependently down\u2010regulated GluN2C\u2009&gt;\u2009GluN2B\u2009&gt;\u2009GluN2A (according to affinity) and attenuated\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine\u2010induced astroglial release of\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamate\/\n                      <jats:sc>d<\/jats:sc>\n                      \u2010serine, dose dependently (GluN2C\u2009&gt;\u2009GluN2A). Chronic exposure (25 \u03bcM)\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine down\u2010regulated GluN2C but increased GluN2C\u2010related astroglial\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamate\/\n                      <jats:sc>d<\/jats:sc>\n                      \u2010serine release. Chronic exposure to &gt;60\u03bcM\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine diminished GluN2C\u2010related astroglial release but activated GluN2A\u2010related release. Chronic administration of 2\u00a0but not 5\u2010mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine restored MK\u2010801\u2010induced decrease sucrose preference.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      Chronic\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine (25\u2009\u03bcM and 2\u00a0mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) down\u2010regulated GluN2C without affecting GluN2A\/GluN2B but increased GluN2\u2010related astroglial\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamate\/\n                      <jats:sc>d<\/jats:sc>\n                      \u2010serine release. Higher\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine dose (&gt;60\u2009\u03bcM; &gt;5\u00a0mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) inactivated GluN2C, but increased GluN2A related astroglial release. These results indicate that dose\u2010dependent activation and inactivation of GluN2C by\n                      <jats:sc>d<\/jats:sc>\n                      \u2010cycloserine is possibly involved in its efficacy on negative symptom of schizophrenia, but with a narrow therapeutic window.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70262","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T02:18:55Z","timestamp":1764382735000},"page":"1602-1622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring effects of chronic\n                    <scp>d<\/scp>\n                    \u2010cycloserine administration on expression of GluN2 subunits and tripartite synaptic transmission in thalamocortical 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