Substitution profiles of N-methyl-D-aspartate antagonists in ethanol-discriminating inbred mice.
Substitution profiles of N-methyl-D-aspartate antagonists in ethanol-discriminating inbred mice.
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N-甲基-D-天冬氨酸拮抗剂在乙醇辨别近交小鼠中的取代谱。
DOI：
10.1016/j.alcohol.2004.07.014
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Shelton,KeithL
中科院分区：
文献类型：
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作者：
Shelton,KeithL
C57 BL/6 J（B6）和DBA/2 J（D2）近交系小鼠在乙醇诱导的行为中显示出明显的差异，例如翻正反射和运动激活的丧失等。他们在条件性位置偏好和口服乙醇的自我管理措施方面也有所不同。在目前的研究中，我检查是否B6和D2小鼠在其表达的N-甲基-D-天冬氨酸（NMDA）受体介导的成分的区别刺激乙醇的影响。训练B6和D2小鼠辨别乙醇（1.5g/kg，i. p.）从生理盐水中提取出来训练完成后，生成乙醇、非竞争性NMDA拮抗剂苯环己哌啶和氯胺酮以及竞争性NMDA拮抗剂d-CPPene的替代和响应率剂量-效应曲线。还生成了咪达唑仑、可卡因、间氯苯哌嗪（mCPP）、吗啡和γ-羟基丁酸（GHB）的剂量-效应曲线。B6和D2小鼠学习了乙醇与盐水的区分。苯环利定在两种菌株中几乎完全取代乙醇，而氯胺酮仅在B6小鼠中完全取代乙醇。d-CPPene在两种菌株中部分取代乙醇。中等剂量的苯环利定在B6小鼠中产生比D2小鼠更大的反应率增加效应，高剂量的苯环利定在D2小鼠中更有效地抑制反应率。相比之下，d-CPPene在两种品系中具有相似的反应率增加作用，但高剂量在B6小鼠中产生更有效的反应率降低作用。在测试的其他药物中，只有咪达唑仑产生了对乙醇的实质性替代。两者合计，这些研究结果似乎表明，NMDA拮抗剂的行为影响不同的菌株之间，但NMDA介导的成分的歧视性刺激效应的乙醇是相似的B6和D2小鼠。
C57BL/6J (B6) and DBA/2J (D2) inbred mice show pronounced differences in ethanol-induced behaviors, such as loss of righting reflex and locomotor activation, among others. They also differ in measures of conditioned place preference and oral self-administration of ethanol. In the current study, I examined whether B6 and D2 mice differed in their expression of the N-methyl-d-aspartate (NMDA) receptor–mediated component of the discriminative stimulus effects of ethanol. B6 and D2 mice were trained to discriminate ethanol (1.5 g/kg, i.p.) from saline in a two-choice, milk-reinforced operant procedure. After training was completed, substitution and response rate dose-effect curves were generated for ethanol; the uncompetitive NMDA antagonists phencyclidine and ketamine; and the competitive NMDA antagonist d-CPPene. Dose-effect curves were also generated for midazolam, cocaine, m-chlorophenylpiperazine (mCPP), morphine, and gamma-hydroxybutyric acid (GHB). B6 and D2 mice learned the ethanol-versus-saline discrimination. Phencyclidine produced near full substitution for ethanol in both strains, whereas ketamine fully substituted for ethanol only in B6 mice. d-CPPene partially substituted for ethanol in both strains. Moderate doses of phencyclidine produced greater response rate–increasing effects in B6 mice than in D2 mice, and high doses of phencyclidine were more potent for suppressing response rates in D2 mice. In contrast, d-CPPene had similar response rate–increasing effects in both strains, but high doses produced more potent response rate–decreasing effects in B6 mice. Among the other drugs tested, only midazolam produced substantial substitution for ethanol. Taken together, these findings seem to indicate that the behavioral effects of NMDA antagonists differ between strains, but that the NMDA-mediated component of the discriminative stimulus effects of ethanol is similar in B6 and D2 mice.