{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:51:34Z","timestamp":1790542294052,"version":"4.1.0"},"reference-count":94,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Fondo Integrativo Speciale per la Ricerca","award":["FISR2019_00202"],"award-info":[{"award-number":["FISR2019_00202"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Endocannabinoid (eCB) signalling is pivotal for brain programming, including the reward system neurodevelopment. Prenatal exposure to \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -tetrahydrocannabinol (THC), cannabis psychoactive component, can perturb eCB tone via CB1 receptor and alter the response to salient stimuli.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>We hypothesise that prenatal THC exposure disrupts the eCB-dopamine nexus in the nucleus accumbens (NAc), predisposing the offspring to excessive alcohol drinking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Using a 3-week intermittent access (IA) two-bottle choice paradigm, we tested binge-like alcohol drinking in prenatally exposed to THC (pTHC) rats of both sexes from early adolescence. NAc gene expression of cannabinoid receptor type 1 (CB1R), eCB enzymatic machinery (DAGL\u03b1,\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), monoacylglycerol lipase (MAGL), fatty-acid amide hydrolase (FAAH)), and D2 receptor was quantified before and after alcohol drinking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>pTHC females consumed higher alcohol levels than controls from the first session onward. In contrast, pTHC males initially drank less than controls but progressively escalated alcohol consumption, although they did not reach females\u2019 drinking levels. Prior to drinking, pTHC females showed increased D2 and DAGL\u03b1 mRNA expression when compared to controls and to pTHC males. pTHC males displayed CB1R upregulation and reduced DAGL\u03b1 expression compared to controls and to pTHC females. Following alcohol drinking, both sexes displayed CB1R downregulation and increased NAPE-PLD expression; pTHC males exhibited DAGL\u03b1 mRNA upregulation; pTHC females showed higher NAPE-PLD expression than pTHC males.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Prenatal THC exposure selectively predisposed the female offspring to alcohol vulnerability. The accumbal insight suggests a D2-driven reduced avoidance pathway in the females and a CB1R-driven avoidance behaviour in the males. Over the IA-paradigm, the potentiation in eCB synthesis plays a critical role in excessive alcohol drinking in pTHC offspring of both sexes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811261420097","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:29:32Z","timestamp":1772245772000},"page":"1493-1505","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Prenatal THC exposure and binge-like alcohol drinking in early adolescence: From sex-specific drinking vulnerability to abnormal endocannabinoid-dopamine nexus in the nucleus accumbens"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-8040","authenticated-orcid":false,"given":"Valentina","family":"Castelli","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1030-9429","authenticated-orcid":false,"given":"Giuseppe","family":"Tringali","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Healthcare Surveillance and Bioethics, Universit\u00e0 Cattolica del Sacro Cuore, Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCSS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4266-7607","authenticated-orcid":false,"given":"Martina","family":"Di Bartolomeo","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4962-379X","authenticated-orcid":false,"given":"Gianluca","family":"Lavanco","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-098X","authenticated-orcid":false,"given":"Claudio","family":"D\u2019Addario","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-8712","authenticated-orcid":false,"given":"Petr","family":"Palivec","sequence":"additional","affiliation":[{"name":"Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czechia"},{"name":"Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7616-6352","authenticated-orcid":false,"given":"Martin","family":"Kuchar","sequence":"additional","affiliation":[{"name":"Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Prague, Czechia"},{"name":"Psychedelics Research Centre, National Institute of Mental Health, Prague, Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-1712","authenticated-orcid":false,"given":"Carla","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-4146","authenticated-orcid":false,"given":"Anna","family":"Brancato","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties \u201cG. D\u2019Alessandro\u201d, University of Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.12.005"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011163"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00220"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2494"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(19990901)33:3<181::AID-SYN3>3.0.CO;2-R"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-47861-8"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301274"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2022.110699"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2020.583122"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881120916135"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9091161"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00031"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.2002.63.91"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13877"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19106152"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02427-6"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2017.00268"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1237485"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15020692"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117699"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.996965"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-013-2456-1"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.10.009"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2021.734975"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05895.x"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2017.01.022"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2022.173358"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14120904"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043907"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105357"},{"key":"e_1_3_2_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2720"},{"key":"e_1_3_2_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-458-2_14"},{"key":"e_1_3_2_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42532-z"},{"key":"e_1_3_2_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2015.08.023"},{"issue":"6","key":"e_1_3_2_36_1","first-page":"459","article-title":"Endocannabinoid-mediated synaptic plasticity and substance use disorders","volume":"37","author":"Fern\u00e1ndez-Espejo E","year":"2022","unstructured":"Fern\u00e1ndez-Espejo E, N\u00fa\u00f1ez-Dom\u00ednguez L (2022) Endocannabinoid-mediated synaptic plasticity and substance use disorders. Neurologia 37(6): 459\u2013465.","journal-title":"Neurologia"},{"issue":"2","key":"e_1_3_2_37_1","article-title":"Sex differences in the neurobiology of alcohol use disorder","volume":"40","author":"Flores-Bonilla A","year":"2020","unstructured":"Flores-Bonilla A, Richardson HN (2020) Sex differences in the neurobiology of alcohol use disorder. Alcohol Research 40(2): 04.","journal-title":"Alcohol Research"},{"key":"e_1_3_2_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-023-00529-4"},{"key":"e_1_3_2_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90087-9"},{"key":"e_1_3_2_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0512-2"},{"key":"e_1_3_2_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2005.01.032"},{"key":"e_1_3_2_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/7268"},{"key":"e_1_3_2_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03344-9"},{"key":"e_1_3_2_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705963"},{"key":"e_1_3_2_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.08.014"},{"key":"e_1_3_2_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2685"},{"key":"e_1_3_2_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2015.06.011"},{"key":"e_1_3_2_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.100"},{"key":"e_1_3_2_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2002.tb02575.x"},{"key":"e_1_3_2_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1165-19.2019"},{"key":"e_1_3_2_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2024.4352"},{"key":"e_1_3_2_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3100"},{"key":"e_1_3_2_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14306"},{"key":"e_1_3_2_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12967"},{"key":"e_1_3_2_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(03)00006-X"},{"key":"e_1_3_2_56_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq5652"},{"key":"e_1_3_2_58_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.1.1.92"},{"key":"e_1_3_2_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2017.06.049"},{"key":"e_1_3_2_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-023-00544-x"},{"key":"e_1_3_2_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2015.02.014"},{"key":"e_1_3_2_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2014.00022"},{"key":"e_1_3_2_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.01.027"},{"key":"e_1_3_2_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn4004"},{"key":"e_1_3_2_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2004.12.003"},{"key":"e_1_3_2_66_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145712001186"},{"key":"e_1_3_2_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12978-020-0880-9"},{"key":"e_1_3_2_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.147"},{"key":"e_1_3_2_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301664"},{"key":"e_1_3_2_70_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0253-22.2022"},{"key":"e_1_3_2_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02190-0"},{"key":"e_1_3_2_72_1","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v42.1.09"},{"key":"e_1_3_2_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01686.x"},{"key":"e_1_3_2_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13923"},{"key":"e_1_3_2_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11829"},{"key":"e_1_3_2_76_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0386-18.2018"},{"issue":"35","key":"e_1_3_2_77_1","article-title":"Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats","volume":"111","author":"Spiga S","year":"2014","unstructured":"Spiga S, Talani G, Mulas G, et al. (2014) Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats. Proceedings of the National Academy of Sciences of the United States of America 111(35): E3745\u2013E3754.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_3_2_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.05.006"},{"key":"e_1_3_2_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.09.014"},{"key":"e_1_3_2_80_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000361"},{"key":"e_1_3_2_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041666"},{"key":"e_1_3_2_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7972"},{"key":"e_1_3_2_83_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187698"},{"key":"e_1_3_2_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2009.11.013"},{"key":"e_1_3_2_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2010.00299.x"},{"key":"e_1_3_2_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04956.x"},{"key":"e_1_3_2_87_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/52908"},{"key":"e_1_3_2_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21073"},{"key":"e_1_3_2_89_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00014.2018"},{"key":"e_1_3_2_90_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0336351100"},{"key":"e_1_3_2_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00020-4"},{"key":"e_1_3_2_92_1","doi-asserted-by":"publisher","DOI":"10.1093\/scan\/nsaa104"},{"key":"e_1_3_2_93_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5217-04.2005"},{"issue":"40","key":"e_1_3_2_94_1","article-title":"Cannabinoid receptor 1-expressing neurons in the nucleus accumbens","volume":"109","author":"Winters BD","year":"2012","unstructured":"Winters BD, Kr\u00fcger JM, Huang X, et al. (2012). Cannabinoid receptor 1-expressing neurons in the nucleus accumbens. Proceedings of the National Academy of Sciences of the United States of America 109(40): E2717\u2013E2725.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_3_2_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.261"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811261420097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02698811261420097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811261420097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T23:29:07Z","timestamp":1787182147000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02698811261420097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":94,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1177\/02698811261420097"],"URL":"https:\/\/doi.org\/10.1177\/02698811261420097","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}