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Glutamate transporters and the glutamate\u2013glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals\/group); 35\u00a0mg\/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15\u00a0days with either valproic acid (VPA, 350\u00a0mg\/kg) or ceftriaxone (CEF, 200\u00a0mg\/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T\n                    <jats:sub>80<\/jats:sub>\n                    ) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real\u2010time polymerase chain reaction (RT\u2010PCR). ECoG measurements showed that the mean spike number of the PTZ\u00a0+\u00a0VPA and PTZ\u00a0+\u00a0CEF groups was significantly lower (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T\n                    <jats:sub>80<\/jats:sub>\n                    ). The expression levels of EAAC1, GLT\u20101, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT\u20101, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced. The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT\u20101 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real\u2010time measurement).\n                  <\/jats:p>","DOI":"10.1111\/1440-1681.13575","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T04:57:29Z","timestamp":1629349049000},"page":"1662-1673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Differential effects of inhibitors of PTZ\u2010induced kindling on glutamate transporters and enzyme expression"],"prefix":"10.1111","volume":"48","author":[{"given":"Numan","family":"Taspinar","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology Faculty of Medicine U\u015fak University U\u015fak Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Hacimuftuoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology Faculty of Medicine Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selcuk","family":"Butuner","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology Faculty of Medicine Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basak","family":"Togar","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques Vocational School of Health Services Bayburt University Bayburt Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokhan","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine Ondokuz May\u0131s University Samsun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Taghizadehghalehjoughi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Veterinary Medicine Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ufuk","family":"Okkay","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology Faculty of Medicine Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdal","family":"Agar","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medicine Ondokuz May\u0131s University Samsun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Turkez","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Faculty of Medicine Atat\u00fcrk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7907","authenticated-orcid":false,"given":"A. 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