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Previous studies have shown that astroglial glutamate transporter\u20101 (GLT\u20101) in the hippocampus and anterior cingulate cortex (ACC) is critically involved in pain processing and modulation. However, the role of astroglial GLT\u20101 in nociceptive pain involving the hippocampus and ACC remains unknown. We investigated the role of 3\u2010[[(2\u2010Methylphenyl) methyl]thio]\u20106\u2010(2\u2010pyridinyl)\u2010pyridazine (LDN\u2010212320), a GLT\u20101 activator, in nociceptive pain model and hippocampal\u2010dependent behavioural tasks in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the effects of LDN\u2010212320 in formalin\u2010induced nociceptive pain model. In addition, formalin\u2010induced impaired hippocampal\u2010dependent behaviours were measured using Y\u2010maze and object recognition test. Furthermore, GLT\u20101 expression and extracellular signal\u2010regulated kinase phosphorylation (pERK1\/2) were measured in the hippocampus and ACC using Western blot analysis and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The LDN\u2010212320 (10 or 20\u00a0mg\/kg, i.p) significantly attenuated formalin\u2010evoked nociceptive behaviour. The antinociceptive effects of LDN\u2010212320 were reversed by systemic administration of DHK (10\u00a0mg\/kg, i.p), a GLT\u20101 antagonist. Moreover, LDN\u2010212320 (10 or 20\u00a0mg\/kg, i.p) significantly reversed formalin\u2010induced impaired hippocampal\u2010dependent behaviour. In addition, LDN\u2010212320 (10 or 20\u00a0mg\/kg, i.p) increased GLT\u20101 expressions in the hippocampus and ACC. On the other hand, LDN\u2010212320 (20\u00a0mg\/kg, i.p) significantly reduced formalin induced\u2010ERK phosphorylation, a marker of nociception, in the hippocampus and ACC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that the GLT\u20101 activator LDN\u2010212320 prevents nociceptive pain by upregulating astroglial GLT\u20101 expression in the hippocampus and ACC. Therefore, GLT\u20101 activator could be a novel drug candidate for nociceptive pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The present study provides new insights and evaluates the role of GLT\u20101 activator in the modulation of nociceptive pain involving hippocampus and ACC. Here, we provide evidence that GLT\u20101 activator could be a potential therapeutic utility for the treatment of nociceptive pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1343","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T16:45:44Z","timestamp":1542213944000},"page":"765-783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Effects of glial glutamate transporter activator in formalin\u2010induced pain behaviour in mice"],"prefix":"10.1002","volume":"23","author":[{"given":"Ghallab","family":"Alotaibi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy South Dakota State University Brookings South Dakota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafiqur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy South Dakota State University Brookings South Dakota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.07.058"},{"issue":"1","key":"e_1_2_8_3_1","first-page":"46","article-title":"NSAID\u2010analgesia, pain control and morbidity in cardiothoracic surgery","volume":"53","author":"Bainbridge, D., Cheng, D. 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