Acute and chronic administration of a low-dose combination of topiramate and ondansetron reduces ethanol's reinforcing effects in male alcohol preferring (P) rats.
Acute and chronic administration of a low-dose combination of topiramate and ondansetron reduces ethanol's reinforcing effects in male alcohol preferring (P) rats.
复制标题
急性和慢性给予托吡酯和昂丹司琼的低剂量组合可降低乙醇对雄性酒精偏好（P）大鼠的增强作用。
DOI：
10.1037/a0035215
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发表时间：
2014
影响因子：
2.3
通讯作者：
Lynch,WendyJ
中科院分区：
文献类型：
--
作者：
Moore,CatherineF;Lycas,MatthewD;Bond,ColinW;Johnson,BankoleA;Lynch,WendyJ
托吡酯（一种GABA/谷氨酸调节剂）和昂丹西琼（一种血清素-3拮抗剂）已显示出治疗酒精使用障碍（AUDs）的希望，尽管这两种药物的疗效一般/不稳定。我们最近在消耗和复发的动物模型中表明，联合使用这些药物的急性治疗比单独使用更有效。为了确定其有益作用的机制是否通过调节乙醇的强化作用，我们在递进比例（PR）计划下测量了这种组合在雄性酒精偏好(P)大鼠（N= 22）中对乙醇的反应。选择不影响（昂丹司琼，0.001 mg/kg）或仅轻微影响（托吡酯，10 mg/kg）酒精相关行为的低剂量，试图最大化其联合疗效，同时最小化潜在副作用。除了急性治疗（1天）外，还检查了慢性给药（10天）的效果，试图模拟人类治疗方法。将联合用药的效果与低剂量托吡酯单独用药进行比较，假设联合用药比单独用药更有效。虽然托吡酯和联合用药在急性治疗后和慢性治疗初期（1-5天）都类似地降低了对乙醇的PR反应，但在重复给药后（6-10天），只有联合用药能持续降低乙醇维持的反应。这些结果表明，与单独使用托吡酯相比，联合使用托吡酯在长期治疗后持续减少乙醇的强化作用方面具有优势，并进一步支持将其用作AUDs的潜在治疗方法。（PsycINFO数据库记录(c) 2019 APA，版权所有）
Topiramate (a GABA/glutamate modulator) and ondansetron (a serotonin-3 antagonist) have shown promise as treatments for alcohol use disorders (AUDs), although efficacy is modest/variable for both medications. We recently showed in animal models of consumption and relapse that acute treatment with a combination of these medications was more efficacious than either alone. To determine whether the mechanism for its beneficial effects is through modulation of ethanol’s reinforcing effects, we measured the effect of this combination in male alcohol preferring (P) rats (N= 22) responding for ethanol under a progressive-ratio (PR) schedule. Low doses, which either do not affect (ondansetron; 0.001 mg/kg) or only modestly affect (topiramate; 10 mg/kg) alcohol-related behaviors on their own, were selected in an attempt to maximize their combined efficacy while minimizing potential side effects. In addition to acute treatment (1 day), the effects of chronic administration (10 days) were examined in an attempt to model human treatment approaches. The effects of the combination were compared with the low dose of topiramate alone hypothesizing that the combination would be more efficacious than topiramate alone. Although both topiramate and the combination similarly reduced PR responding for ethanol following acute treatment and during the initial phase of chronic treatment (Days 1–5), after repeated administration (Days 6–10), only the combination produced a sustained reduction in ethanol-maintained responding. These results suggest an advantage of the combination over topiramate alone at producing a sustained reduction in ethanol’s reinforcing effects following prolonged treatment, and lend further support for its use as a potential treatment for AUDs.(PsycINFO Database Record (c) 2019 APA, all rights reserved)