{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:19:24Z","timestamp":1787026764838,"version":"build-2736575974"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>\n                    Despite evidence that supports cannabidiol (CBD) as an anticonvulsant agent, there remains controversy over the antiseizure efficacy, possible adverse effects, and synergistic interactions with classic antiepileptics such as valproate (VPA). The genetic audiogenic seizure hamster from the University of Salamanca (GASH\/Sal) is a reliable experimental model of generalized tonic\u2013clonic seizures in response to intense sound stimulation. The present study examines the behavioral and molecular effects of acute and chronic intraperitoneal administrations of VPA (300 mg\/kg) and CBD (100 mg\/kg) on the GASH\/Sal audiogenic seizures, as well as the coadministration of both drugs. The GASH\/Sal animals were examined prior to and after the corresponding treatment at 45 min, 7 days, and 14 days for seizure severity and neuroethology, open-field behaviors, body weight variations, and various hematological and biochemical parameters. Furthermore, the brain tissue containing the inferior colliculus (so-called epileptogenic nucleus) was processed for reverse transcription\u2013quantitative polymerase chain reaction analysis to determine the treatment effects on the gene expression of neuronal receptors associated with drug actions and ictogenesis. Our results indicated that single dose of VPA helps prevent the animals from getting convulsions, showing complete elimination of seizures, whereas 7 days of chronic VPA treatment had few effects in seizure behaviors. Acute CBD administration showed subtle attenuation of seizure behaviors, increasing seizure latency and decreasing the duration of the convulsion phase, but without entirely seizure abolition. Chronic CBD treatments had no significant effects on sound-induced seizures, although some animals slightly improved seizure severity. Acute and chronic CBD treatments have no significant adverse effects on body weight, hematological parameters, and liver function, although locomotor activity was reduced. The combination of VPA and CBD did not alter the therapeutic outcome of the VPA monotherapy, showing no apparent synergistic effects. As compared to sham animals, chronic treatments with CBD caused abnormal mRNA expression levels for\n                    <jats:italic>Trpv1, Adora1, Slc29a1<\/jats:italic>\n                    , and\n                    <jats:italic>Cnr1<\/jats:italic>\n                    genes, whereas no differences in gene expression were found for\n                    <jats:italic>Htr1a<\/jats:italic>\n                    and\n                    <jats:italic>Sigmar1<\/jats:italic>\n                    . Our study shed light on the behavioral and molecular effects of CBD and VPA on the GASH\/Sal model and constituted the basis to develop further studies on the pharmacological effects of CBD and its interactions with other anticonvulsants.\n                  <\/jats:p>","DOI":"10.3389\/fnbeh.2020.612624","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T23:36:46Z","timestamp":1611272206000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Behavioral and Molecular Effects Induced by Cannabidiol and Valproate Administration in the GASH\/Sal Model of Acute Audiogenic Seizures"],"prefix":"10.3389","volume":"14","author":[{"given":"Giselda","family":"Cabral-Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"S\u00e1nchez-Benito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.","family":"D\u00edaz-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Sancho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando","family":"Castellano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis J.","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores E.","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"G\u00f3mez-Nieto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR Data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"Andersen","year":"2004","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.yebeh.2013.05.028","article-title":"Pharmacological and neuroethological studies of three antiepileptic drugs in the genetic audiogenic seizure hamster (GASH:Sal)","volume":"28","author":"Barrera-Bail\u00f3n","year":"2013","journal-title":"Epilepsy Behav."},{"key":"B3","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.yebeh.2015.11.005","article-title":"Pharmacological and neuroethological study of the acute and chronic effects of lamotrigine in the genetic audiogenic seizure hamster (GASH:Sal)","volume":"71","author":"Barrera-Bail\u00f3n","year":"2017","journal-title":"Epilepsy Behav."},{"key":"B4","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/cmdc.200800442","article-title":"Synthesis and pharmacological activity of a potent inhibitor of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol","volume":"4","author":"Bisogno","year":"2009","journal-title":"ChemMedChem"},{"key":"B5","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.neuropharm.2015.08.046","article-title":"Adenosinergic signaling in epilepsy","volume":"104","author":"Boison","year":"2016","journal-title":"Neuropharmacology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"106594","DOI":"10.1016\/j.yebeh.2019.106594","article-title":"Molecular tools for the characterization of seizure susceptibility in genetic rodent models of epilepsy","volume":"1","author":"Bosque","year":"2019","journal-title":"Epilepsy Behav."},{"key":"B7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1472-6750-5-31","article-title":"Standardisation of data from real-time quantitative PCR methods - 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