{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:35:40Z","timestamp":1790728540097,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2018,8,9]],"date-time":"2018-08-09T00:00:00Z","timestamp":1533772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","award":["1674"],"award-info":[{"award-number":["1674"]}],"id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Autism spectrum disorder (ASD) is more commonly diagnosed in males than in females. Prenatal exposure to the antiepileptic drug valproic acid (VPA) is an environmental risk factor of ASD. Male rats prenatally exposed to VPA show socio\u2010emotional autistic\u2010like dysfunctions that have been related to changes in the activity of the endocannabinoid anandamide. Here, we have investigated if prenatal VPA induced sex\u2010specific autistic endophenotypes involving anandamide signalling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We studied sex\u2010specific differences in the ASD\u2010like socio\u2010emotional, cognitive and repetitive symptoms displayed during development of Wistar rats of both sexes, prenatally exposed to VPA. The involvement of anandamide was followed by Western blotting of cannabinoid CB\n                      <jats:sub>1<\/jats:sub>\n                      receptors and by inhibiting its metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Female rats were less vulnerable to the deleterious effects of prenatal VPA exposure on social communication, emotional reactivity and cognitive performance than male rats. Conversely, as observed in male rats, prenatal VPA exposure induced selective deficits in social play behaviour and stereotypies in the female rat offspring. At the neurochemical level, prenatal VPA exposure altered phosphorylation of CB\n                      <jats:sub>1<\/jats:sub>\n                      receptors in a sex\u2010specific, age\u2010specific and tissue\u2010specific manner. Enhancing anandamide signalling through inhibition of its degradation reversed the behavioural deficits displayed by VPA\u2010exposed animals of both sexes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings highlight sexually dimorphic consequences of prenatal VPA exposure that may be related to sex\u2010specific effects of VPA on endocannabinoid neurotransmission in the course of development and introduce a new therapeutic target for reversing autistic\u2010like symptoms in both sexes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14435","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T01:40:17Z","timestamp":1530582017000},"page":"3699-3712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Sex\u2010specific autistic endophenotypes induced by prenatal exposure to valproic acid involve anandamide signalling"],"prefix":"10.1111","volume":"175","author":[{"given":"Francesca","family":"Melancia","sequence":"first","affiliation":[{"name":"Department of Science, Section of Biomedical Sciences and Technologies University \u2018Roma Tre\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Schiavi","sequence":"additional","affiliation":[{"name":"Department of Science, Section of Biomedical Sciences and Technologies University \u2018Roma Tre\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Servadio","sequence":"additional","affiliation":[{"name":"Department of Science, Section of Biomedical Sciences and Technologies University \u2018Roma Tre\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Cartocci","sequence":"additional","affiliation":[{"name":"Department of Science, Section of Biomedical Sciences and Technologies University \u2018Roma Tre\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Campolongo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u2018V. 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