Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl-d-aspartate receptor-ion channel complex, not via sigma1 receptors

Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl-d-aspartate receptor-ion channel complex, not via sigma1 receptors
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苯环己哌啶诱导的辨别刺激是通过 N-甲基-d-天冬氨酸受体-离子通道复合物上的苯环己哌啶结合位点介导的,而不是通过 sigma1 受体介导

DOI:
10.1016/s0166-4328(00)00333-8
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发表时间:
2001
影响因子:
2.7
通讯作者:
T. Nabeshima
T. Nabeshima
中科院分区:
心理学3区
文献类型:
--
作者:
Akitomo Mori;Y. Noda;T. Mamiya;Y. Miyamoto;A. Nakajima;H. Furukawa;T. Nabeshima

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在训练辨别PCP(1.5 mg/kg,i. p.)的大鼠中,研究了几种N-甲基-d-天冬氨酸(NMDA)受体和σ受体相关化合物对苯环己哌啶(PCP)辨别刺激效应的影响。在两个杠杆固定比率20的食物强化方案下从盐水中获得。五氯苯酚产生了剂量依赖性增加五氯苯酚适当的反应。非竞争性NMDA受体拮抗剂地佐环平(0.2mg/kg,i. p.)和推定的σ 1受体激动剂(+)-SKF-10047(10 mg/kg,i. p.)在每只测试的老鼠身上都完全替代了五氯苯酚。竞争性NMDA受体拮抗剂CGS-19755(0.1-3 mg/kg,i. p.),σ 1受体激动剂,(+)-喷他佐辛(10-30 mg/kg,i. p.)去甲美沙芬(10-20 mg/kg,i. p.)产生类似PCP的辨别刺激效应。五氯酚(1.5mg/kg,i. p.)地佐环平(0.2mg/kg,i. p.)和(+)-SKF-10047(10 mg/kg,i.p.)CGS-19755(1 mg/kg,i. p.)显著减弱,而σ 1受体拮抗剂BMY-14802(10 mg/kg,i. p.)和NE-100(5mg/kg,i.p.)。这些结果表明,PCP的歧视性刺激效应主要是通过PCP的NMDA受体离子通道复合物上的结合位点介导的,而不是通过sigma 1受体。此外,(+)-SKF-10047的PCP样辨别刺激效应被证明是通过PCP结合位点介导的。
The effects of several N-methyl-d-aspartate (NMDA) receptor- and sigma receptor-related compounds on the discriminative stimulus effects of phencyclidine (PCP) were examined in rats trained to discriminate PCP (1.5 mg/kg, i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. PCP produced a dose-dependent increase in PCP-appropriate responding. A non-competitive NMDA receptor antagonist, dizocilpine (0.2 mg/kg, i.p.) and a putative sigma1receptor agonist, (+)-SKF-10047 (10 mg/kg, i.p.) fully substituted for PCP in every rat tested. Neither a competitive NMDA receptor antagonist, CGS-19755 (0.1–3 mg/kg, i.p.), sigma1receptor agonist, (+)-pentazocine (10–30 mg/kg, i.p.) nor dextromethorphan (10–20 mg/kg, i.p.) produced PCP-like discriminative stimulus effects. The discriminative stimulus effects of PCP (1.5 mg/kg, i.p.), dizocilpine (0.2 mg/kg, i.p.) and (+)-SKF-10047 (10 mg/kg, i.p.) were significantly attenuated by CGS-19755 (1 mg/kg, i.p.), but not by sigma1receptor antagonist BMY-14802 (10 mg/kg, i.p.) and NE-100 (5 mg/kg, i.p.). These results suggest that the discriminative stimulus effects of PCP are predominantly mediated via PCP binding sites on the NMDA receptor-ion channel complex, not via sigma1receptors. In addition, the PCP-like discriminative stimulus effects of (+)-SKF-10047 were demonstrated to be mediated via PCP binding sites.
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