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首页> 外文期刊>Addiction biology >The glycine reuptake inhibitor Org24598 and acamprosate reduce ethanol intake in the rat; Tolerance development to acamprosate but not to Org24598
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The glycine reuptake inhibitor Org24598 and acamprosate reduce ethanol intake in the rat; Tolerance development to acamprosate but not to Org24598

机译：甘氨酸再摄取抑制剂Org24598和阿坎酸降低了大鼠的乙醇摄入;耐受性发展到阿坎酸而不是Org24598

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Extracellular glycine modulates accumbal dopamine levels as well as ethanol-induced dopamine overflow. Glycine availability is also crucial for regulating alcohol consumption and the glycine transporter 1 (GlyT-1) inhibitor Org25935 robustly decreases alcohol intake in rats. To explore whether the alcohol-intake reducing effect of Org25935 is substance bound, we examined the effect of a different selective GlyT-1 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 a ethanol preference in a limited access two bottle free-choice model for 12 days, followed by alcohol deprivation for 14 days before a second test period of 10 days. Finally, rats underwent in vivo microdialysis where dopamine, glycine, taurine and β-alanine in n. accumbens 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-induced dopamine response in n. accumbens. The study demonstrates a robust anti-alcohol intake effect of the GlyT-1 inhibitor Org24598, supporting the new concept that GlyT-1 inhibition reduces ethanol consumption. GlyT-1 inhibition may represent a new treatment principle for alcoholism that is superior to acamprosate.
机译：细胞外甘氨酸调节累积多巴胺水平以及乙醇诱导的多巴胺溢出。甘氨酸的可用性对于调节酒精消耗也至关重要，而甘氨酸转运蛋白1（GlyT-1）抑制剂Org25935会强烈降低大鼠的酒精摄入量。为了探讨Org25935减少酒精摄入的作用是否与物质结合，我们研究了另一种选择性GlyT-1抑制剂Org24598对大鼠乙醇消耗的影响，并将其与目前正在临床使用的药物阿坎酸（Acamprosate）的作用进行了比较。 。我们在有限选择两瓶免费选择模型中研究了每日Org24598和阿坎酸注射液对有乙醇偏爱的雄性Wistar大鼠的作用，为期12天，然后进行酒精剥夺14天，然后进行第二次测试，为期10天。最后，大鼠进行体内微透析，其中n在多巴胺，甘氨酸，牛磺酸和β-丙氨酸中。测量伏隔。 Org24598大大减少了乙醇的摄入，并且在两个治疗期中效果一直保持。 Acamprosate迅速减少了乙醇的摄入，但是在第三天对这种作用产生了耐受性，而acamprosate在第二个测试期间未能影响酒精的摄入。 Org24598和阿坎酸都不会减少水分摄入。饮酒研究后，Org24598组的基础伏安多巴胺水平高于阿坎酸和赋形剂组。 Org24598和阿坎酸都降低了乙醇诱导的多巴胺反应。伏击。该研究证明了GlyT-1抑制剂Org24598具有很强的抗酒精摄入作用，支持了GlyT-1抑制作用减少乙醇消耗的新概念。 GlyT-1抑制可能代表了优于阿坎酸的新的酒精中毒治疗原理。

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