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The major objective of the study was to assess the impact of acute nicotine on neuronal and astrocytic metabolic activity in the prefrontal cortex, cerebral cortex and hippocampus of awake mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Nicotine (0.0125\u20132.00\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) was administered subcutaneously to 2\u2010 to 2.5\u2010month\u2010old C57BL\/6NCrl male mice. The neuronal and astrocytic metabolic activity was measured by infusing [1,6\u2010\n                      <jats:sup>13<\/jats:sup>\n                      C\n                      <jats:sub>2<\/jats:sub>\n                      ]glucose and [2\u2010\n                      <jats:sup>13<\/jats:sup>\n                      C]acetate, respectively, 15\u2009min after injection, and monitoring amino acids labelling in the\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010[\n                      <jats:sup>13<\/jats:sup>\n                      C]\u2010NMR spectrum of brain tissue extracts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Nicotine perturbed glucose metabolism in a dose\u2010 and brain\u2010\u2009region\u2010dependent manner. At lower doses, it enhanced the rate of glucose oxidation in glutamatergic neurons in the hippocampus (0.0125\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) and prefrontal cortex (0.025\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), with no change in the cerebral cortex. In contrast, a higher nicotine dose (1.0\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) suppressed glutamatergic and GABAergic neurometabolic activity in all three brain regions. Nicotine did not affect the astrocytic metabolic activity at the lower dose (0.025\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) but suppressed it at the high dose (2.0\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Nicotine has biphasic impacts on glutamatergic activity, enhancing excitatory activity at low doses but reducing both excitatory and inhibitory activity at higher doses. Most interestingly, acute nicotine increases neuronal excitability by shifting the excitation\u2010to\u2010inhibition balance in the prefrontal cortex, a critical component of the mesocortical circuitry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70242","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:18:37Z","timestamp":1764566317000},"page":"1860-1877","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biphasic effect of nicotine on glutamatergic activity in male mouse brain"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5912-5440","authenticated-orcid":false,"given":"Prajakta Pramod","family":"Biyani","sequence":"first","affiliation":[{"name":"NMR Microimaging and Spectroscopy CSIR \u2013 Centre for Cellular and Molecular Biology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-946X","authenticated-orcid":false,"given":"Ajay","family":"Sarawagi","sequence":"additional","affiliation":[{"name":"NMR Microimaging and Spectroscopy CSIR \u2013 Centre for Cellular and Molecular Biology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-9395","authenticated-orcid":false,"given":"Anant Bahadur","family":"Patel","sequence":"additional","affiliation":[{"name":"NMR Microimaging and Spectroscopy CSIR \u2013 Centre for Cellular and Molecular Biology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.795"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12407"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12377.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094742"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb09067.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24572"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.48"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyu011"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.701170"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-10-03864.2000"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703991"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.77"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2008.04.009"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050069n"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14595"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.001313"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10348"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.05967.x"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1761"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15210"},{"issue":"1","key":"e_1_2_13_24_1","first-page":"4","article-title":"Neuronal mechanisms underlying development of nicotine dependence: Implications for novel smoking\u2010cessation treatments","volume":"6","author":"D'Souza M. 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