Bienkowski P, Stefanski R, Kostowski W
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Alcohol. 1997 Jul-Aug;14(4):345-50. doi: 10.1016/s0741-8329(96)00181-4.
Several drug discrimination studies reported that both competitive and uncompetitive NMDA receptor antagonists substituted for ethanol stimulus in rats. In the present study we examined if compounds that act as agonists at the NMDA receptor complex, D-cycloserine (a partial agonist at the glycine positive modulatory site) and N-methyl-D-aspartate (an agonist at the glutamate binding site), could antagonize the discriminative stimulus effects of ethanol. Rats were trained to discriminate between IP administered 1.0 g/kg of ethanol (10% v/v) and saline under a sweetened milk-reinforced fixed ratio 10 (FR10) schedule of reinforcement. When the animals met the discriminative criteria, antagonism tests were conducted with D-cycloserine (0.3-10.0 mg/kg, IP) and N-methyl-D-aspartate (15.0-60.0 mg/kg, IP). Neither D-cycloserine nor N-methyl-D-aspartate antagonized the ethanol-mediated discriminative stimulus effects. In addition, D-cycloserine (3.0-300.0 mg/kg, IP) did not substitute for ethanol. These results indicate that at least certain agonists at the NMDA receptor complex do not attenuate the ethanol interoceptive cue in the rat.
多项药物辨别研究报告称，竞争性和非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂均可替代大鼠体内的乙醇刺激。在本研究中，我们检验了作为NMDA受体复合物激动剂的化合物，即D-环丝氨酸（甘氨酸正向调节位点的部分激动剂）和N-甲基-D-天冬氨酸（谷氨酸结合位点的激动剂）是否能够拮抗乙醇的辨别刺激效应。大鼠接受训练，在加糖牛奶强化的固定比例10（FR10）强化程序下，辨别腹腔注射1.0 g/kg乙醇（10% v/v）和生理盐水。当动物达到辨别标准时，用D-环丝氨酸（0.3 - 10.0 mg/kg，腹腔注射）和N-甲基-D-天冬氨酸（15.0 - 60.0 mg/kg，腹腔注射）进行拮抗试验。D-环丝氨酸和N-甲基-D-天冬氨酸均未拮抗乙醇介导的辨别刺激效应。此外，D-环丝氨酸（3.0 - 300.0 mg/kg，腹腔注射）不能替代乙醇。这些结果表明，至少某些NMDA受体复合物激动剂不会减弱大鼠体内的乙醇内感受性线索。
