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首页> 外文期刊>Psychopharmacology >Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice.
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Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice.

机译：氨基金刚烷类NMDA受体拮抗剂对日程诱发的酒精和小鼠自食水的行为影响。

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RATIONALE: Aminoadamantanes represent a class of NMDA glutamate receptor antagonists that reduce alcohol consumption and may prevent alcohol-induced neuronal adaptations and side effects. OBJECTIVE: Behavioral specificity of memantine and amantadine on alcohol drinking in a schedule-induced polydipsia (SIP) task was investigated in mice. METHODS: Male C57BL/6J mice were food-deprived and divided into four groups: 5% alcohol SIP, water SIP, 1 h limited access regulatory water drinking, and a control group to determine if either drug altered ethanol drinking. Behavioral specificity of memantine (5, 10, and 25 mg/kg, ip) and amantadine (20, 40, and 60 mg/kg, ip) was determined by comparing alterations in alcohol or water consumption in SIP and regulatory water drinking. Drug effects on SIP drinking-specific measures (grams per kilogram consumption) were also compared to nondrinking measures (locomotion, head-entries for food, and lick efficiency). RESULTS: Compared to saline, memantine reduced alcohol SIPdrinking (10 and 25 mg/kg). Memantine increased locomotion during alcohol SIP (25 mg/kg) and during water SIP (5 and 25 mg/kg). In contrast, amantadine reduced both alcohol SIP (40 mg/kg) and water SIP (40 and 60 mg/kg). Both drugs reduced regulatory water consumption over the entire dose range tested. Blood alcohol concentrations indicated consumption of physiologically meaningful amounts of alcohol during SIP, and that changes in alcohol metabolism did not account for drug-induced reductions in alcohol drinking. CONCLUSIONS: In addition to reducing alcohol drinking, both drugs had other behavioral effects that included reductions in regulatory drinking. These results suggest that the therapeutic utility of these drugs for ameliorating human alcohol addiction remains questionable.
机译：理由：氨基金刚烷类代表一类NMDA谷氨酸受体拮抗剂，可减少酒精消耗并可能阻止酒精引起的神经元适应和副作用。目的：研究美金刚和金刚烷胺在日程诱发的多饮（SIP）任务中对饮酒的行为特异性。方法：雄性C57BL / 6J小鼠被禁食，分为四组：5％酒精SIP，水SIP，1小时有限获取调节饮水和对照组，以确定是否有一种药物改变了乙醇饮水。美金刚（5、10和25 mg / kg，腹腔注射）和金刚烷胺（20、40和60 mg / kg，腹腔注射）的行为特异性是通过比较SIP和规范饮水中酒精或水消耗的变化来确定的。还比较了对SIP特定饮酒措施（每公斤消费克数）的药物作用与非饮酒措施（运动，进食食物和舔食效率）的比较。结果：与盐水相比，美金刚减少了酒精的SIP饮用量（10和25 mg / kg）。美金刚在酒精SIP（25 mg / kg）和水SIP（5和25 mg / kg）期间增加运动。相比之下，金刚烷胺同时降低了酒精SIP（40 mg / kg）和水SIP（40和60 mg / kg）。两种药物在整个测试剂量范围内均减少了调节水的消耗。血液中的酒精浓度表明在SIP期间消耗了生理上有意义的酒精，并且酒精代谢的变化并未说明药物引起的饮酒量减少。结论：除减少饮酒外，两种药物还具有其他行为作用，包括减少监管饮酒。这些结果表明，这些药物在改善人类酒精成瘾方面的治疗效用仍然值得怀疑。

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