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Across multiple preclinical models of early adversity, there are reports of astrocyte dysfunction and disrupted amino acid neurotransmission, along with maladaptive behavioral responses in adulthood. Disrupted G protein\u2010coupled receptor signaling is known to phenocopy specific consequences of early\u2010life adversity. Enhanced Gq signaling in the forebrain excitatory neurons in early postnatal life programs anxio\u2010depressive behaviors in adulthood, accompanied by altered neuronal glutamate and GABA metabolism in mouse models. We hypothesized that enhancing Gq signaling in forebrain excitatory neurons in early postnatal life may also impact astrocyte function in adulthood. Our results show that postnatal hM3Dq\u2010mediated chemogenetic activation of CaMKII\u03b1\u2010positive forebrain excitatory neurons not only increases anxiety\u2010like behavior but also evokes bidirectional transcriptional regulation of multiple astrocyte\u2010associated genes in the neocortex and hippocampi. While\n                    <jats:italic>Gfap<\/jats:italic>\n                    ,\n                    <jats:italic>Aldh1l1<\/jats:italic>\n                    ,\n                    <jats:italic>Eaat1<\/jats:italic>\n                    , and\n                    <jats:italic>Eaat3<\/jats:italic>\n                    mRNA levels were reduced in the neocortex, they were enhanced in the hippocampus, and a similar pattern was noted for GFAP protein levels. Chronic postnatal chemogenetic activation of CaMKII\u03b1\u2010positive neurons did not alter astrocyte cell density in both the neocortex and the hippocampus. Using (\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010(\n                    <jats:sup>13<\/jats:sup>\n                    C)) NMR spectroscopy, we observed a significant decline in astrocyte\u2010specific glutamate and GABA neurotransmitter turnover, and a reduction in astrocyte metabolic flux within the neocortex and hippocampus in adulthood in animals with a history of postnatal chemogenetic activation of forebrain excitatory neurons. Our findings indicate that chemogenetically driving Gq signaling chronically during the postnatal window in forebrain excitatory neurons results in persistent changes well into adulthood, with enhanced anxiety\u2010like behaviors and disrupted astrocyte function and metabolism, phenocopying specific changes in astrocyte function noted following early adversity.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70702","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:50:37Z","timestamp":1791348637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Postnatal Chemogenetic Activation of Forebrain Excitatory Neurons Modulates Astrocyte\u2010Associated Function and Metabolism in Adult Male Mice"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-8404","authenticated-orcid":false,"given":"Amartya","family":"Pradhan","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Tata Institute of Fundamental Research  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sthitapranjya","family":"Pati","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Tata Institute of Fundamental Research  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Saba","sequence":"additional","affiliation":[{"name":"Council of Scientific and Industrial Research\u2013Centre for Cellular and Molecular Biology  Hyderabad Telangana India"},{"name":"Academy of Scientific and Innovative Research  Ghaziabad Uttar Pradesh 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