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To explore whether the alcohol\u2010intake reducing effect of Org25935 is substance bound, we examined the effect of a different selective GlyT\u20101 inhibitor, Org24598, on ethanol consumption in rats and compared the effect with that of acamprosate, a drug currently in clinical use. We studied the effects of daily Org24598 and acamprosate injections on male Wistar rats with \u223c60% ethanol preference in a limited access two bottle free\u2010choice model for 12 days, followed by alcohol deprivation for 14 days before a second test period of 10 days. Finally, rats underwent <jats:italic>in vivo<\/jats:italic> microdialysis where dopamine, glycine, taurine and \u03b2\u2010alanine in n.\u2003accumbens were measured. Org24598 profoundly reduced ethanol intake and the effect remained throughout both treatment periods. Acamprosate promptly reduced ethanol intake, but on the third day tolerance developed to this effect and acamprosate failed to influence alcohol consumption during the second test period. Neither Org24598 nor acamprosate reduced water intake. Following the drinking study, the Org24598 group displayed higher basal accumbal dopamine levels compared with acamprosate and vehicle groups. Both Org24598 and acamprosate reduced the ethanol\u2010induced dopamine response in n.\u2003accumbens. The study demonstrates a robust anti\u2010alcohol intake effect of the GlyT\u20101 inhibitor Org24598, supporting the new concept that GlyT\u20101 inhibition reduces ethanol consumption. GlyT\u20101 inhibition may represent a new treatment principle for alcoholism that is superior to acamprosate.<\/jats:p>","DOI":"10.1111\/j.1369-1600.2011.00367.x","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T16:49:15Z","timestamp":1317228555000},"page":"897-907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The glycine reuptake inhibitor Org24598 and acamprosate reduce ethanol intake in the rat; tolerance development to acamprosate but not to Org24598"],"prefix":"10.1111","volume":"17","author":[{"given":"Helga H.","family":"Lid\u00f6","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Marston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Ericson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"S\u00f6derpalm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340055"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/34.2.175"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(01)00355-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbm083"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01063.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01062.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/13556210500223132"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04680.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4927(98)00016-X"},{"key":"e_1_2_7_11_1","first-page":"483","article-title":"Ethanol and acamprosate increase the extracellular taurine in the nucleus accumbens: a microdialysis experiment","volume":"30","author":"Dahchour A","year":"1995","journal-title":"Alcohol Alcoholism"},{"key":"e_1_2_7_12_1","first-page":"485","article-title":"Acute ethanol increases taurine but neither glutamate nor GABA in the nucleus accumbens of male rats: a microdialysis study","volume":"29","author":"Dahchour A","year":"1994","journal-title":"Alcohol Alcohol"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200519060-00004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.7966"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00602-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04868.x"},{"key":"e_1_2_7_17_1","unstructured":"GeJ HamiltonM CollieI ShahidM HillD WalkerG(1998)Differential modulation of glycine re\u2010uptake inhibitor (GUI) on glycine levels in brain regions of freely moving rats in vivo. 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