{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:54:56Z","timestamp":1787900096814,"version":"build-2784847793"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Certain events that occur in early life, such as changes in nutrition, can induce structural and functional modifications in brain development, leading to behavioral programing in the offspring. These effects depend on the timing, intensity, and duration of exposure, and may contribute to chronic disorders in adulthood. Artificial non-nutritive sweeteners (NNS), such as saccharin, have recently been proposed as potential developmental disruptors. Saccharin consumption during pregnancy is discouraged, as it can cross the placenta and accumulate in the fetus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, pregnant rats were administered 0.1% saccharin in drinking water throughout gestation. On postnatal day 21, offspring were assessed for behavioral outcomes using the open field and elevated plus maze tests. During sacrifice, the prefrontal cortex of the animals was collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Gestational saccharin exposure induced sex-specific behavioral changes: offspring of saccharin-consuming mothers spent more time in the center of the arena, while only females showed increased open-arm entries. These alterations were coupled with changes in prefrontal endocannabinoid, glutamatergic, and GABAergic gene expression. Only saccharin-exposed male pups showed significant alterations in Dagla, Daglb and Gpr55 along with increased expression of glutamatergic receptors (\n                      <jats:italic>Grin1, Grin2a, Grin2c, Gria1, Grm3<\/jats:italic>\n                      ). Females exhibited reduced expression of GABAergic receptor genes (\n                      <jats:italic>Gabrg2, Gabbr2<\/jats:italic>\n                      ), and significant changes in the phosphorylated expression of proteins involved in the insulin pathway (IRS-1, PI3K, AKT, GSK3b).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that developmental NNS exposure produces long-lasting behavioral outcomes in offspring, which are linked to alterations in multiple signaling pathways within the prefrontal cortex.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1815692","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:41:29Z","timestamp":1777527689000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-term consequences of prenatal saccharin exposure: evidence of sex-specific molecular programing in the prefrontal cortex and behavior of adolescent rats"],"prefix":"10.3389","volume":"20","author":[{"given":"Beatriz","family":"Pacheco-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental. Hospital Universitario de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"L\u00f3pez-Merch\u00e1n","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Rubio","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Garc\u00eda-Martos","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda Humana","place":["Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"Departamento de Anatom\u00eda Humana","place":["Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Sanjuan","sequence":"additional","affiliation":[{"name":"Euronutra S.L.","place":["M\u00e1laga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Rubio","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"Departamento de Anatom\u00eda Humana","place":["Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Mart\u00edn-de-Las-Heras","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"Departamento de Anatom\u00eda Humana","place":["Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Rodr\u00edguez de Fonseca","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Neurolog\u00eda, Hospital Regional Universitario de M\u00e1laga","place":["M\u00e1laga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Al\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Psicobiolog\u00eda, Facultad de Psicolog\u00eda, Universidad Complutense de Madrid","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialuisa","family":"de Ceglia","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental. Hospital Universitario de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rivera","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma Bionand, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga","place":["M\u00e1laga, Spain"]},{"name":"Departamento de Anatom\u00eda Humana","place":["Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"107633","DOI":"10.1016\/j.neuropharm.2019.05.010","article-title":"Brain insulin action in schizophrenia: something borrowed and something new.","volume":"163","author":"Agarwal","year":"2020","journal-title":"Neuropharmacology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"E156","DOI":"10.1152\/ajpendo.00642.2020","article-title":"Insulin action in the brain regulates both central and peripheral functions.","volume":"321","author":"Agrawal","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1007\/s00213-016-4219-8","article-title":"The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats.","volume":"233","author":"Aliczki","year":"2016","journal-title":"Psychopharmacology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1177\/0269881117704986","article-title":"2-Arachidonoylglycerol endocannabinoid signaling coupled to metabotropic glutamate receptor type-5 modulates anxiety-like behavior in the rat ventromedial prefrontal cortex.","volume":"31","author":"Almeida-Santos","year":"2017","journal-title":"J. Psychopharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nrn.2017.45","article-title":"Adult hippocampal neurogenesis and cognitive flexibility \u2014 linking memory and mood.","volume":"18","author":"Anacker","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.conb.2011.12.006","article-title":"Regulation of AMPA receptor trafficking and synaptic plasticity.","volume":"22","author":"Anggono","year":"2012","journal-title":"Curr. Opin. Neurobiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"884","DOI":"10.3390\/biom14080884","article-title":"Impact of serotonin transporter absence on brain insulin receptor expression, plasma metabolome changes, and ADHD-like behavior in mice fed a western diet.","volume":"14","author":"Anthony","year":"2024","journal-title":"Biomolecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.neubiorev.2004.03.004","article-title":"Regional dissociations within the hippocampus\u2013memory and anxiety.","volume":"28","author":"Bannerman","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"419","DOI":"10.3390\/brainsci12040419","article-title":"Keeping the Balance: GABA(B) receptors in the developing brain and beyond.","volume":"12","author":"Bassetti","year":"2022","journal-title":"Brain Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0006-8993(00)02986-3","article-title":"Glutamate in the parabrachial nucleus of rats during conditioned taste aversion.","volume":"887","author":"Bielavska","year":"2000","journal-title":"Brain Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"552","DOI":"10.7334\/psicothema2016.383","article-title":"Non-normal data: Is ANOVA still a valid option?","volume":"29","author":"Blanca","year":"2017","journal-title":"Psicothema"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.neuron.2015.03.042","article-title":"The GABA receptor as a therapeutic target for neurodevelopmental disorders.","volume":"86","author":"Braat","year":"2015","journal-title":"Neuron"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1111\/ejn.12995","article-title":"Adolescent-onset GABAA \u03b11 silencing regulates reward-related decision making.","volume":"42","author":"Butkovich","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"803394","DOI":"10.3389\/fpsyt.2021.803394","article-title":"Cell-type specific deletion of cb2 cannabinoid receptors in dopamine neurons induced hyperactivity phenotype: possible relevance to attention-deficit hyperactivity disorder.","volume":"12","author":"Canseco-Alba","year":"2022","journal-title":"Front. Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neuron.2012.09.020","article-title":"Endocannabinoid signaling and synaptic function.","volume":"76","author":"Castillo","year":"2012","journal-title":"Neuron"},{"key":"B16","first-page":"e201908052","article-title":"Non-caloric sweeteners in pregnancy and lactation].","volume":"93","author":"Cavagnari","year":"2019","journal-title":"Rev. Esp. Salud Publica"},{"key":"B17","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.tins.2022.03.001","article-title":"Insulin action in the brain: cell types, circuits, and diseases.","volume":"45","author":"Chen","year":"2022","journal-title":"Trends Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"ENEURO.0011-15.2015","DOI":"10.1523\/eneuro.0011-15.2015","article-title":"Role of GPR55 during Axon growth and target innervation.","volume":"2","author":"Cherif","year":"2015","journal-title":"eNeuro"},{"key":"B19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1749-8104-5-7","article-title":"Insulin receptor signaling in the development of neuronal structure and function.","volume":"5","author":"Chiu","year":"2010","journal-title":"Neural Dev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s00424-013-1258-4","article-title":"Gender differences in neurodevelopment and epigenetics.","volume":"465","author":"Chung","year":"2013","journal-title":"Pflugers Arch."},{"key":"B21","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.neuron.2008.03.001","article-title":"Behavioral phenotyping strategies for mutant mice.","volume":"57","author":"Crawley","year":"2008","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1007\/s00125-016-3996-2","article-title":"Cerebral cortex: a target and source of insulin?","volume":"59","author":"Csajb\u00f3k","year":"2016","journal-title":"Diabetologia"},{"key":"B23","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jpeds.2016.05.013","article-title":"The role of nutrition in brain development: the golden opportunity of the \u201cFirst 1000 Days\u201d.","volume":"175","author":"Cusick","year":"2016","journal-title":"J. Pediatr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.neubiorev.2004.09.006","article-title":"Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates.","volume":"28","author":"Dalley","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1038\/s41380-023-02065-4","article-title":"Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.","volume":"28","author":"de Bartolomeis","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.3390\/ph14101002","article-title":"Obesity as a condition determined by food addiction: Should brain endocannabinoid system alterations be the cause and its modulation the solution?","volume":"14","author":"de Ceglia","year":"2021","journal-title":"Pharmaceuticals"},{"key":"B27","doi-asserted-by":"publisher","first-page":"458","DOI":"10.2174\/1570159x23666241107160840","article-title":"Cafeteria diet abstinence induces depressive behavior and disrupts endocannabinoid signaling in dopaminergic areas: a preclinical study.","volume":"23","author":"de Ceglia","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"746437","DOI":"10.3389\/fped.2021.746437","article-title":"Maternal sweeteners intake modulates gut microbiota and exacerbates learning and memory processes in adult male offspring.","volume":"9","author":"de la Garza","year":"2021","journal-title":"Front. Pediatr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.neuroscience.2020.09.030","article-title":"Role of neuropeptide S on behavioural and neurochemical changes of an animal model of attention-deficit\/hyperactivity disorder.","volume":"448","author":"de Santana Souza","year":"2020","journal-title":"Neuroscience"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.yfrne.2015.08.001","article-title":"Early life origins of metabolic disease: developmental programming of hypothalamic pathways controlling energy homeostasis.","volume":"39","author":"Dearden","year":"2015","journal-title":"Front. Neuroendocrinol."},{"key":"B31","first-page":"102","article-title":"Insulin and the brain.","volume":"9","author":"Derakhshan","year":"2013","journal-title":"Curr. Diabetes Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"925792","DOI":"10.3389\/fnins.2022.925792","article-title":"Cannabinoid type-2 receptors: an emerging target for regulating schizophrenia-relevant brain circuits.","volume":"16","author":"Ferranti","year":"2022","journal-title":"Front. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/s0166-4328(01)00292-3","article-title":"Factors controlling measures of anxiety and responses to novelty in the mouse.","volume":"125","author":"File","year":"2001","journal-title":"Behav. Brain Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"17009","DOI":"10.3390\/ijms242317009","article-title":"The effect of fat intake with increased omega-6-to-omega-3 polyunsaturated fatty acid ratio in animal models of early and late Alzheimer\u2019s Disease-like pathogenesis.","volume":"24","author":"Galeano","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/j.1476-5381.2011.01625.x","article-title":"Chronic blockade of cannabinoid CB2 receptors induces anxiolytic-like actions associated with alterations in GABA(A) receptors.","volume":"165","author":"Garc\u00eda-Guti\u00e9rrez","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/978-3-319-20825-1_13","article-title":"Endocannabinoids and metabolic disorders.","volume":"231","author":"Gatta-Cherifi","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"432","DOI":"10.3390\/genes10060432","article-title":"Sex differences in the epigenome: a cause or consequence of sexual differentiation of the brain?","volume":"10","author":"Gegenhuber","year":"2019","journal-title":"Genes"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e348","DOI":"10.1002\/wdev.348","article-title":"Signatures of sex: sex differences in gene expression in the vertebrate brain.","volume":"9","author":"Gegenhuber","year":"2020","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1113\/jphysiol.2014.273763","article-title":"Molecular bases of NMDA receptor subtype-dependent properties.","volume":"593","author":"Glasgow","year":"2015","journal-title":"J. Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1093\/cercor\/bhab274","article-title":"Prolonged consumption of sweetened beverages lastingly deteriorates cognitive functions and reward processing in mice.","volume":"32","author":"Hamelin","year":"2022","journal-title":"Cereb. Cortex"},{"key":"B41","doi-asserted-by":"publisher","first-page":"152327","DOI":"10.1016\/j.tox.2019.152327","article-title":"Gestational and perinatal exposure to diazinon causes long-lasting neurobehavioral consequences in the rat.","volume":"429","author":"Hawkey","year":"2020","journal-title":"Toxicology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1111\/ejn.12485","article-title":"Brain \u03b3-aminobutyric acid: a neglected role in impulsivity.","volume":"39","author":"Hayes","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"648780","DOI":"10.3389\/fnbeh.2021.648780","article-title":"Perinatal stress and methamphetamine exposure decreases anxiety-like behavior in adult male rats.","volume":"15","author":"Holubov\u00e1-Kroupov\u00e1","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1093\/ijnp\/pyac067","article-title":"Role of appetite hormone dysregulation in symptomology and executive function in adolescents with attention deficit hyperactivity disorder.","volume":"26","author":"Hsu","year":"2022","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s11033-024-09374-z","article-title":"Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.","volume":"51","author":"Iqbal","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.neubiorev.2018.12.026","article-title":"Progress in brain cannabinoid CB(2) receptor research: from genes to behavior.","volume":"98","author":"Jordan","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/978-3-030-57369-0_9","article-title":"Psychiatric disorders and cannabinoid receptors.","volume":"1264","author":"Joshi","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2183\/pjab.90.235","article-title":"Control of synaptic function by endocannabinoid-mediated retrograde signaling.","volume":"90","author":"Kano","year":"2014","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1146\/annurev-neuro-062111-150420","article-title":"Multiple functions of endocannabinoid signaling in the brain.","volume":"35","author":"Katona","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.bbr.2013.04.043","article-title":"Alterations in the endocannabinoid system in the rat valproic acid model of autism.","volume":"249","author":"Kerr","year":"2013","journal-title":"Behav. Brain Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.1073\/pnas.1500877112","article-title":"Insulin resistance in brain alters dopamine turnover and causes behavioral disorders.","volume":"112","author":"Kleinridders","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B52","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3389\/fnmol.2020.00088","article-title":"Dysregulated prefrontal cortex inhibition in prepubescent and adolescent fragile X mouse model.","volume":"13","author":"Kramvis","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1080\/15592294.2015.1114202","article-title":"Maternal immune activation induces GAD1 and GAD2 promoter remodeling in the offspring prefrontal cortex.","volume":"10","author":"Labouesse","year":"2015","journal-title":"Epigenetics"},{"key":"B54","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00424-010-0809-1","article-title":"Glutamate receptors, neurotoxicity and neurodegeneration.","volume":"460","author":"Lau","year":"2010","journal-title":"Pfl\u00fcgers Archiv - Eur. J. Physiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nrn2153","article-title":"NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders.","volume":"8","author":"Lau","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.molmet.2016.06.011","article-title":"Insulin in the nervous system and the mind: functions in metabolism, memory, and mood.","volume":"5","author":"Lee","year":"2016","journal-title":"Mol. Metab."},{"key":"B57","doi-asserted-by":"publisher","first-page":"76","DOI":"10.31083\/j.fbl2703076","article-title":"Consequences of diabetes and pre-diabetes and the role of biochemical parameters of carbohydrate metabolism for the functioning of the prefrontal cortex in obese patients.","volume":"27","author":"Lesiewska","year":"2022","journal-title":"Front. Biosci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.biopsych.2021.06.002","article-title":"Maternal metabolic programming of the developing central nervous system: unified pathways to metabolic and psychiatric disorders.","volume":"91","author":"Lippert","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"B59","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/dom.12337","article-title":"Control of brain development and homeostasis by local and systemic insulin signalling.","volume":"16","author":"Liu","year":"2014","journal-title":"Diabetes Obes Metab."},{"key":"B60","doi-asserted-by":"publisher","first-page":"229","DOI":"10.31887\/DCNS.2020.22.3\/rmaldonado","article-title":"The endocannabinoid system in modulating fear, anxiety, and stress.","volume":"22","author":"Maldonado","year":"2020","journal-title":"Dialogues Clin. Neurosci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"114139","DOI":"10.1016\/j.bcp.2020.114139","article-title":"Galantamine improves enhanced impulsivity, impairments of attention and long-term potentiation induced by prenatal nicotine exposure to mice.","volume":"180","author":"Mamiya","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"653384","DOI":"10.3389\/fcell.2021.653384","article-title":"Exposure to prenatal stress is associated with an excitatory\/inhibitory imbalance in rat prefrontal cortex and amygdala and an increased risk for emotional dysregulation.","volume":"9","author":"Marchisella","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"771","DOI":"10.2174\/1570159x14666160729155441","article-title":"Advances in the physiology of GPR55 in the central nervous system.","volume":"15","author":"Marichal-Cancino","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"13532","DOI":"10.1523\/jneurosci.0847-08.2008","article-title":"The endocannabinoid 2-arachidonoylglycerol is responsible for the slow self-inhibition in neocortical interneurons.","volume":"28","author":"Marinelli","year":"2008","journal-title":"J. Neurosci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/s41380-022-01812-3","article-title":"Insulin modulates emotional behavior through a serotonin-dependent mechanism.","volume":"29","author":"Martin","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"B66","doi-asserted-by":"publisher","first-page":"462","DOI":"10.23736\/s0026-4946.20.05981-2","article-title":"Nutrition and growth in children.","volume":"72","author":"Matonti","year":"2020","journal-title":"Minerva Pediatr."},{"key":"B67","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.neubiorev.2014.02.006","article-title":"A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior.","volume":"42","author":"McLaughlin","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B68","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/ijo.2015.209","article-title":"Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity.","volume":"40","author":"Meadows","year":"2016","journal-title":"Int. J. Obes."},{"key":"B69","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41593-020-00752-x","article-title":"GABAergic signaling to astrocytes in the prefrontal cortex sustains goal-directed behaviors.","volume":"24","author":"Mederos","year":"2021","journal-title":"Nat. Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"114806","DOI":"10.1016\/j.bbr.2023.114806","article-title":"Sex-specific variations in spatial reference memory acquisition: insights from a comprehensive behavioral test battery in C57BL\/6JRj mice.","volume":"459","author":"Melgar-Locatelli","year":"2024","journal-title":"Behav. Brain Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1097\/FBP.0b013e32834eb04a","article-title":"Effects of developmental nicotine exposure in rats on decision-making in adulthood.","volume":"23","author":"Mitchell","year":"2012","journal-title":"Behav. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"105729","DOI":"10.1016\/j.phrs.2021.105729","article-title":"The endocannabinoidome in neuropsychiatry: opportunities and potential risks.","volume":"170","author":"Morris","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.tins.2020.01.002","article-title":"Early adversity and critical periods: neurodevelopmental consequences of violating the expectable environment.","volume":"43","author":"Nelson","year":"2020","journal-title":"Trends Neurosci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.3389\/fmicb.2019.01360","article-title":"Maternal exposure to non-nutritive sweeteners impacts progeny\u2019s metabolism and microbiome.","volume":"10","author":"Olivier-Van Stichelen","year":"2019","journal-title":"Front. Microbiol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.ijdevneu.2008.09.002","article-title":"Characteristic behavioral anomalies in rats prenatally exposed to 5-bromo-2\u2019-deoxyuridine.","volume":"27","author":"Orito","year":"2009","journal-title":"Int. J. Dev. Neurosci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13293-025-00724-5","article-title":"Gestational saccharin consumption disrupts gut-brain axis glucose homeostasis control in adolescent offspring rats in a sex-dependent manner.","volume":"16","author":"Pacheco-S\u00e1nchez","year":"2025","journal-title":"Biol. Sex Differ."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1038\/npp.2011.51","article-title":"Schizophrenia-like attentional deficits following blockade of prefrontal cortex GABAA receptors.","volume":"36","author":"Paine","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"B78","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ejphar.2007.02.013","article-title":"Increased sensitivity of adolescent spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder, to the locomotor stimulation induced by the cannabinoid receptor agonist WIN 55,212-2.","volume":"563","author":"Pandolfo","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"B79","author":"Paxinos","year":"2007","journal-title":"The Rat Brain in Stereotaxic Coordinates"},{"key":"B80","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3390\/life11030262","article-title":"Brain insulin resistance: focus on insulin receptor-mitochondria interactions.","volume":"11","author":"Pomytkin","year":"2021","journal-title":"Life"},{"key":"B81","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/fnbeh.2016.00208","article-title":"Maternal caloric restriction implemented during the preconceptional and pregnancy period alters hypothalamic and hippocampal endocannabinoid levels at birth and induces overweight and increased adiposity at adulthood in male rat offspring.","volume":"10","author":"Ram\u00edrez-L\u00f3pez","year":"2016","journal-title":"Front. Behav. Neurosci."},{"key":"B82","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1080\/1028415X.2020.1821519","article-title":"Maternal hypercaloric diet affects factors involved in lipid metabolism and the endogenous cannabinoid systems in the hypothalamus of adult offspring: sex-specific response of astrocytes to palmitic acid and anandamide.","volume":"25","author":"Rivera","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.3390\/nu12061829","article-title":"Sex-specific anxiety and prefrontal cortex glutamatergic dysregulation are long-term consequences of pre-and postnatal exposure to hypercaloric diet in a rat model.","volume":"12","author":"Rivera","year":"2020","journal-title":"Nutrients"},{"key":"B84","doi-asserted-by":"publisher","first-page":"110703","DOI":"10.1016\/j.pnpbp.2022.110703","article-title":"Acute intrahippocampal administration of melanin-concentrating hormone impairs memory consolidation and decreases the expression of MCHR-1 and TrkB receptors.","volume":"123","author":"Ruiz-Viroga","year":"2022","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B85","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fnbeh.2017.00015","article-title":"Effects of intermittent alcohol exposure on emotion and cognition: a potential role for the endogenous cannabinoid system and neuroinflammation.","volume":"11","author":"Sanchez-Marin","year":"2017","journal-title":"Front. Behav. Neurosci."},{"key":"B86","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/s2213-8587(20)30161-3","article-title":"Gestational diabetes: opportunities for improving maternal and child health.","volume":"8","author":"Saravanan","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1744-9081-7-11","article-title":"Effects of early life trauma are dependent on genetic predisposition: a rat study.","volume":"7","author":"Sterley","year":"2011","journal-title":"Behav. Brain Funct."},{"key":"B88","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fendo.2011.00054","article-title":"Insulin signaling and autism.","volume":"2","author":"Stern","year":"2011","journal-title":"Front. Endocrinol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nature13793","article-title":"Artificial sweeteners induce glucose intolerance by altering the gut microbiota.","volume":"514","author":"Suez","year":"2014","journal-title":"Nature"},{"key":"B90","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neulet.2016.09.020","article-title":"Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia.","volume":"633","author":"Sz\u00fccs","year":"2016","journal-title":"Neurosci. Lett."},{"key":"B91","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.3390\/nu13093278","article-title":"Maternal fructose diet-induced developmental programming.","volume":"13","author":"Thompson","year":"2021","journal-title":"Nutrients"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1021\/acsptsci.4c00105","article-title":"Hydroxytyrosol linoleoyl ether ameliorates metabolic-associated fatty liver disease symptoms in obese zucker rats.","volume":"7","author":"Tovar","year":"2024","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"B93","doi-asserted-by":"publisher","first-page":"6292","DOI":"10.3390\/ijms22126292","article-title":"Analysis of both lipid metabolism and endocannabinoid signaling reveals a new role for hypothalamic astrocytes in maternal caloric restriction-induced perinatal programming.","volume":"22","author":"Tovar","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B94","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.biopsych.2014.09.007","article-title":"Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.","volume":"77","author":"Tse","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00008877-200202000-00001","article-title":"Behavioural and pharmacological relevance of stroke-prone spontaneously hypertensive rats as an animal model of a developmental disorder.","volume":"13","author":"Ueno","year":"2002","journal-title":"Behav. Pharmacol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3389\/fendo.2014.00241","article-title":"Sex-specific differences in lipid and glucose metabolism.","volume":"5","author":"Varlamov","year":"2014","journal-title":"Front. Endocrinol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuint.2018.12.002","article-title":"Involvement of catecholaminergic and GABAAergic mediations in the anxiety-related behavior in long-term powdered diet-fed mice.","volume":"124","author":"Yaoita","year":"2019","journal-title":"Neurochem. Int."},{"key":"B98","doi-asserted-by":"publisher","first-page":"4857","DOI":"10.1113\/jphysiol.2011.212225","article-title":"Postsynaptic diacylglycerol lipase mediates retrograde endocannabinoid suppression of inhibition in mouse prefrontal cortex.","volume":"589","author":"Yoshino","year":"2011","journal-title":"J. Physiol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.biopha.2018.11.039","article-title":"Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: the role of CB2 and PPAR-\u03b3 receptors.","volume":"110","author":"Youssef","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"B100","doi-asserted-by":"publisher","first-page":"e0198064","DOI":"10.1371\/journal.pone.0198064","article-title":"Attention and working memory deficits in a perinatal nicotine exposure mouse model.","volume":"13","author":"Zhang","year":"2018","journal-title":"PLoS One"}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2026.1815692\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:41:31Z","timestamp":1777527691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2026.1815692\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":100,"alternative-id":["10.3389\/fnbeh.2026.1815692"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2026.1815692","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"article-number":"1815692"}}