Koros E, Kostowski W, Danysz W, Bienkowski P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 1999 Feb;359(2):117-22. doi: 10.1007/pl00005330.
There is a large body of experimental evidence that both stress and N-methyl-D-aspartate (NMDA) receptor antagonists may alter acute behavioural effects of ethanol. Notably, an uncompetitive, low-affinity NMDA receptor antagonist, memantine, has been recently claimed to possess anti-craving properties in rats with a long-term history of ethanol consumption. The aim of the present study was to assess the effects of restraint stress and memantine on the dose-response curve of ethanol discrimination. Rats were trained to discriminate 1 g/kg ethanol from saline in the two-lever drug discrimination procedure. When ethanol discrimination was acquired, the subjects were exposed to 30-min sessions of acute restraint stress, and different doses of ethanol (0.25, 0.5 or 1 g/kg) or saline were administered. In subsequent experiments the effects of memantine (2.25 or 4.5 mg/kg) on the cueing effects of ethanol were tested. Neither the stress sessions nor memantine influenced the ethanol discrimination dose-response curve. Moreover, the stress did not alter the rate of responding. However, both doses of memantine tended to increase the rate of responding when given in combination with lower doses of ethanol (0.25-0.5 g/kg). In contrast, 4.5 mg/kg memantine decreased the response rate when combined with 1 g/kg ethanol. These results suggest that: (1) pre-exposure to acute restraint stress or memantine does not affect the dose-response curve of ethanol discrimination; (2) memantine given in combination with low doses of ethanol may stimulate operant behaviour in the food-reinforced drug discrimination procedure.
大量实验证据表明，应激和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂均可能改变乙醇的急性行为效应。值得注意的是，一种非竞争性、低亲和力的NMDA受体拮抗剂美金刚，最近被宣称在有长期乙醇摄入史的大鼠中具有抗渴求特性。本研究的目的是评估束缚应激和美金刚对乙醇辨别剂量反应曲线的影响。在双杠杆药物辨别程序中，训练大鼠区分1 g/kg乙醇和生理盐水。当获得乙醇辨别能力后，让实验对象接受30分钟的急性束缚应激，并给予不同剂量的乙醇（0.25、0.5或1 g/kg）或生理盐水。在随后的实验中，测试了美金刚（2.25或4.5 mg/kg）对乙醇提示效应的影响。应激实验和美金刚均未影响乙醇辨别剂量反应曲线。此外，应激并未改变反应率。然而，当与较低剂量的乙醇（0.25 - 0.5 g/kg）联合使用时，两种剂量的美金刚均倾向于提高反应率。相反，4.5 mg/kg美金刚与1 g/kg乙醇联合使用时降低了反应率。这些结果表明：（1）急性束缚应激或美金刚的预先暴露不影响乙醇辨别剂量反应曲线；（2）美金刚与低剂量乙醇联合使用可能会在食物强化药物辨别程序中刺激操作性行为。
