靶向甘氨酸摄取治疗酒精觅药和复饮。
Targeting Glycine Reuptake in Alcohol Seeking and Relapse.
机构信息
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (V.V., M.R., T.T.T., R.S.); Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Basel, Switzerland (D.A.); Department of Pharmacology, Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany (B.B., A.B.); and Department of Psychopharmacology, Pavlov Medical University, St. Petersburg, Russia (A.B.)
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (V.V., M.R., T.T.T., R.S.); Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Basel, Switzerland (D.A.); Department of Pharmacology, Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany (B.B., A.B.); and Department of Psychopharmacology, Pavlov Medical University, St. Petersburg, Russia (A.B.).
出版信息
J Pharmacol Exp Ther. 2018 Apr;365(1):202-211. doi: 10.1124/jpet.117.244822. Epub 2018 Jan 24.
It has recently been demonstrated that pharmacological blockade of the glycine transporter 1 (GlyT1) reduced alcohol intake and relapse in rats. The aim of the present study was to further explore the role of GlyT1 in alcohol relapse-like behavior. For this purpose we used three different GlyT1 blockers-SSR504734, A-1246399, and RO4993850-and tested their effect on alcohol-seeking and relapse-like consumption. Two behavioral models, the alcohol deprivation effect model and the cue-induced reinstatement model, were used. Our data show that all three GlyT1 blockers reduce relapse-like alcohol consumption and cause either minimal or no side effects, measured as changes in home-cage activity, water intake, and body weight. In the reinstatement test, GlyT1 blockers completely abolished alcohol-seeking responses. Furthermore, we tested other drug/cue associations and found that cocaine-seeking responses were also abolished by GlyT1 blockade. Our data confirm that GlyT1 can be used as a target to develop novel anticraving and antirelapse drugs.
最近的研究表明，抑制甘氨酸转运体 1（GlyT1）的药理学方法可以减少大鼠的酒精摄入量和复发。本研究旨在进一步探讨 GlyT1 在酒精复发样行为中的作用。为此，我们使用了三种不同的 GlyT1 阻断剂-SSR504734、A-1246399 和 RO4993850-并测试了它们对酒精寻求和复发样消费的影响。我们使用了两种行为模型，即酒精剥夺效应模型和线索诱导复吸模型。我们的数据表明，所有三种 GlyT1 阻断剂都可以减少复发样的酒精消费，并且几乎没有或没有副作用，通过测量笼内活动、饮水量和体重的变化来衡量。在复吸测试中，GlyT1 阻断剂完全消除了酒精寻求反应。此外，我们还测试了其他药物/线索关联，发现可卡因寻求反应也被 GlyT1 阻断所消除。我们的数据证实，GlyT1 可以作为开发新型抗渴求和抗复发药物的靶点。
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