{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:09:08Z","timestamp":1783642148414,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pharmacological research in the field of pharmacokinetics, neuropsychopharmacology, and on-cology\u201d (MUNI\/A\/1249\/2020) with the support of the Specific University Research at Masaryk University provided by the Ministry of Education, Youth and Sports of the","award":["MUNI\/A\/1249\/2020"],"award-info":[{"award-number":["MUNI\/A\/1249\/2020"]}]},{"name":"SoMoPro II Programme","award":["3SGA5789"],"award-info":[{"award-number":["3SGA5789"]}]},{"name":"Piano triennale per la Ricerca - Linea Intervento 2, Bando\u201d CHANCE\u201c- Linea Intervento 1 and Starting Grant 2020, University of Catania","award":["Not available"],"award-info":[{"award-number":["Not available"]}]},{"name":"FARDIB UniTe project","award":["not available"],"award-info":[{"award-number":["not available"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist\/inverse agonist AM251 (0.5 mg\/kg\/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.<\/jats:p>","DOI":"10.3390\/biom12010108","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T17:42:25Z","timestamp":1641836545000},"page":"108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia"],"prefix":"10.3390","volume":"12","author":[{"given":"Tibor","family":"Stark","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic"},{"name":"Scientific Core Unit Neuroimaging, Max Planck Institute of Psychiatry, 80804 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-8370","authenticated-orcid":false,"given":"Fabio Arturo","family":"Iannotti","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Di Martino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Di Bartolomeo","sequence":"additional","affiliation":[{"name":"Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-0799","authenticated-orcid":false,"given":"Jana","family":"Ruda-Kucerova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-4622","authenticated-orcid":false,"given":"Fabiana","family":"Piscitelli","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten T.","family":"Wotjak","sequence":"additional","affiliation":[{"name":"Central Nervous System Diseases Research (CNSDR), Boehringer Ingelheim Pharma GmbH & Co KG, 88397 Biberach an der Riss, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"D\u2019Addario","sequence":"additional","affiliation":[{"name":"Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Drago","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-3070","authenticated-orcid":false,"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy"},{"name":"Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Faculty of Medicine and Faculty of Agricultural and Food Sciences, Centre de Recherche de l\u2019Institut de Cardiologie et Pneumologie de l\u2019Universit\u00e9 et Institut sur la Nutrition et les Aliments Fonctionnels, Centre NUTRISS, Universit\u00e9 Laval, Quebec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Micale","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/mp.2012.23","article-title":"Neurodevelopmental model of schizophrenia: Update","volume":"17","author":"Rapoport","year":"2012","journal-title":"Mol. 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