{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:13:18Z","timestamp":1758759198723,"version":"3.44.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Valproate may hold promise as a treatment for addiction. However, there are limited studies examining the effects of magnesium valproate (VPA\u2010Mg) on methamphetamine (MA) addiction, and the relevant mechanisms have not been thoroughly discussed. This study aims to explore the potential therapeutic effects of VPA\u2010Mg on MA addiction and to investigate its possible mechanisms. The effects of VPA\u2010Mg on MA addiction were investigated using conditioned place preference (CPP) and behavioural sensitisation models in rats. VPA\u2010Mg was administered during CPP formation and extinction phases to evaluate its effects on MA\u2010induced CPP formation and reinstatement. Behavioural sensitisation assessed the impact of VPA\u2010Mg during sensitisation induction and expression phases, with spontaneous activity and MA dosing optimised beforehand. Furthermore, western blotting was performed on brain regions including the prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) to measure glycogen synthase kinase 3 beta (GSK\u20103\u03b2) and dopamine transporter (DAT) protein levels. VPA\u2010Mg did not exhibit a significant impact on MA\u2010induced CPP formation. VPA\u2010Mg significantly reduced the establishment and expression of MA\u2010induced behavioural sensitisation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Pre\u2010treatment with VPA\u2010Mg for 3 days before the expression period also inhibited sensitisation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In addition, the ratio of p\u2010GSK\u20103\u03b2 to t\u2010GSK\u20103\u03b2 in the PFC, Hip and VTA of rats with behavioural sensitisation significantly decreased, and the expression of DAT decreased significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). VPA\u2010Mg can reverse the increase in GSK\u20103\u03b2 activity in the Hip and the decrease in DAT in the PFC and Hip caused by repeated MA use (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). VPA\u2010Mg exhibits anti\u2010addictive effects on MA dependence and relapse prevention. GSK\u20103\u03b2 activation and DAT downregulation in addiction\u2010related brain regions (PFC, Hip, VTA) are closely linked to MA addiction, suggesting potential therapeutic targets. VPA\u2010Mg may exert its effects by modulating these pathways, particularly in the PFC and Hip.<\/jats:p>","DOI":"10.1111\/adb.70084","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:46:54Z","timestamp":1758545214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect and Mechanism of Magnesium Valproate on Methamphetamine\u2010Addicted Rats"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4755-563X","authenticated-orcid":false,"given":"Yuanrong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Psychiatry, and National Clinical Research Center for Mental Disorders The Second Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Anhui No. 2 Provincial People's Hospital  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, and National Clinical Research Center for Mental Disorders The Second Xiangya Hospital of Central South University  Changsha Hunan 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