{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:07:21Z","timestamp":1792976841468,"version":"4.5.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA029674"],"award-info":[{"award-number":["AA029674"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ethanol consumption disrupts glutamate homeostasis in several brain regions. The uptake of extracellular glutamate is regulated in the majority by the astrocytic glutamate transporter 1 (GLT-1), and cystine-glutamate exchanger (xCT) contributes to this regulatory effect. Chronic ethanol consumption is well known to downregulate GLT-1 expression in several reward brain regions, including the nucleus accumbens (NAc).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Recently, we reported that a novel beta-lactam, MC-100093, attenuated ethanol consumption and normalized the expression of GLT-1 in the subregions of the NAc. Based on these findings, we aimed in this study to determine the dose-dependent effect of MC-100093 in attenuating ethanol consumption and whether this attenuating effect is associated with restoration of glutamate uptake. In addition, we focused on whether the effects of MC-100093 on GLT-1 are mediated through the mammalian target of rapamycin (mTOR), protein kinase B (Akt), and nuclear factor-kappa B (NF-\u03baB) signaling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female alcohol-preferring (P) rats are grouped into 4 groups. Other than control groups all the 3 groups had free access to ethanol (15% and 30% v\/v), and water for 5 weeks. On week 6, rats received intraperitoneal injection (i.p.) of MC-100093 at a dosage of 100 or 150\u00a0mg\/kg, or saline, for 5 days. The Na+ dependent and Na+ independent glutamate uptake is measured by radioactive glutamate uptake assay. The expression of GLT-1, xCT, mTOR, phospho-Akt (p-Akt), kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBa), and NF-\u03baB are determined by Western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MC-100093 treatment reduced ethanol drinking in male and female P rats. MC-100093 was associated with an increase in Na+-dependent and Na+-independent glutamate uptake. Furthermore, MC-100093 treatment attenuated ethanol-induced decrease in GLT-1, xCT, NF-\u03baB, and p-Akt expression in the NAc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that MC-100093 attenuated ethanol consumption and regulated glutamate uptake through normalizing GLT-1 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf075","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:29:15Z","timestamp":1759750155000},"source":"Crossref","is-referenced-by-count":8,"title":["Modulatory effects of GLT-1 enhancer, MC-100093, on glutamate uptake and associated signaling pathways in female and male alcohol preferring rats exposed to ethanol"],"prefix":"10.1093","volume":"28","author":[{"given":"Ahmed","family":"Alotaibi","sequence":"first","affiliation":[{"name":"Department of 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Shareef","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Temple University School of Pharmacy , Philadelphia, PA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magid","family":"Abou-Gharbia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Temple University School of Pharmacy , Philadelphia, PA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Childers","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Temple University School of Pharmacy , Philadelphia, PA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-9786","authenticated-orcid":false,"given":"Youssef","family":"Sari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental 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