{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:13:23Z","timestamp":1790324003459,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["444682\/2023\u20106"],"award-info":[{"award-number":["444682\/2023\u20106"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Adolescent cannabis exposure has been associated with an increased risk of schizophrenia; however, how genetic vulnerability shapes the long\u2010term consequences of adolescent cannabinoid exposure remains poorly understood. \u0394\n 9<\/jats:sup>\n \u2010Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis and the predominant cannabinoid in the THC\u2010rich cannabis extract used here, primarily activates cannabinoid type 1 receptors (CB1). In parallel, reduced availability of D\u2010serine, an endogenous co\u2010agonist of N\u2010methyl\u2010D\u2010aspartate receptors (NMDARs), has been implicated in the pathophysiology of schizophrenia. Here, we investigated whether adolescent exposure to a THC\u2010rich cannabis extract modulated long\u2010term behavioral, neurochemical, and glial outcomes in serine racemase mutant (SrrY269*) mice, a genetic model characterized by reduced D\u2010serine levels and schizophrenia\u2010relevant phenotypes. Mice received escalating oral doses of the THC\u2010rich cannabis extract during adolescence and were evaluated in adulthood using behavioral assays, amino acid quantification, and glial morphometric analyses. Adolescent exposure to the THC\u2010rich cannabis extract prevented deficits in prepulse inhibition and spatial object recognition memory in adult SrrY269* mice, while transiently impairing sensorimotor gating in wild\u2010type animals. Irrespective of genotype, mice exposed to the THC\u2010rich cannabis extract spent more time in the center of the open field in adulthood. In behaviorally tested SrrY269* mice, reduced hippocampal microglial branching was attenuated following adolescent treatment. In an independent behavior\u2010na\u00efve cohort, SrrY269* mice exhibited marked astrocytic morphological alterations, several of which were also attenuated by adolescent exposure to the THC\u2010rich cannabis extract. In contrast, the same treatment induced a distinct astrocytic phenotype in wild\u2010type mice. Adolescent exposure to the THC\u2010rich cannabis extract did not alter hippocampal or prefrontal cortical levels of D\u2010serine or other amino acids involved in NMDAR signaling in adulthood. These findings indicate that adolescent exposure to a THC\u2010rich cannabis extract produces genotype\u2010dependent long\u2010term effects, preventing specific behavioral deficits and attenuating independently assessed microglial and astrocytic alterations in SrrY269* mice, while producing adverse behavioral and astrocytic outcomes in wild\u2010type animals. Genetic background may therefore be an important determinant of the long\u2010term neurodevelopmental consequences of adolescent exposure to THC\u2010rich cannabis extracts.\n <\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>","DOI":"10.1111\/jnc.70559","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:02:10Z","timestamp":1790319730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adolescent Exposure to a\n THC<\/scp>\n \u2010Rich Cannabis Extract Produces Genotype\u2010Dependent Effects on Cognition and Glial Morphology in Serine Racemase Mutant Mice"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9133-1558","authenticated-orcid":false,"given":"Igor F.","family":"Rangel","sequence":"first","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1608-0875","authenticated-orcid":false,"given":"Melissa","family":"Chaves","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5352-7671","authenticated-orcid":false,"given":"Iohanna","family":"Pagnoncelli","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5972-1260","authenticated-orcid":false,"given":"Isabelle","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5751-2142","authenticated-orcid":false,"given":"Felipe","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-6447","authenticated-orcid":false,"given":"Lorena","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4543-3577","authenticated-orcid":false,"given":"Luiza","family":"Castello\u2010Branco","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-6539","authenticated-orcid":false,"given":"Ernesto Diaz","family":"Roch","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-9101","authenticated-orcid":false,"given":"Virg\u00ednia Martins","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-9235","authenticated-orcid":false,"given":"Flavia Regina Souza","family":"Lima","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6755-9840","authenticated-orcid":false,"given":"Rog\u00e9rio","family":"Panizzutti","sequence":"additional","affiliation":[{"name":"Instituto de Psiquiatria Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-4983","authenticated-orcid":false,"given":"Luciana","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1007\/s00213-019-5171-1","article-title":"Adolescent Exposure to \u03949\u2010Tetrahydrocannabinol Delays Acquisition of 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