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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Decrement in operant performance produced by NMDA receptor antagonists in the rat: tolerance and cross-tolerance.
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Decrement in operant performance produced by NMDA receptor antagonists in the rat: tolerance and cross-tolerance.

机译：NMDA受体拮抗剂在大鼠中产生的操作性能下降：耐受性和交叉耐受性。

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摘要

Current perspectives on the clinical use of NMDA receptor antagonists infer repeated administration schedules for the management of different pathological states. The development of tolerance and cross-tolerance between different NMDA receptor antagonists may be an important factor contributing to the clinical efficacy of these drugs. The present study aimed to characterize the development of tolerance and cross-tolerance to the ability of various site-selective NMDA receptor antagonists to produce a decrement of operant responding (multiple extinction 9 s fixed-interval 1-s schedule of water reinforcement). Acute administration of D-CPPen (SDZ EAA 494; 1-5.6 mg/kg), dizocilpine (MK-801; 0.03-0.3 mg/kg), memantine (0.3-17 mg/kg), ACEA-1021 (10-56 mg/kg), and eliprodil (1-30 mg/kg) differentially affected operant responding. Both increases and decreases in response rates and accuracy of responding were observed. Repeated preexposure to D-CPPen (5.6 mg/kg, once a day for 7 days) attenuated a behavioral disruption produced by an acute challenge with D-CPPen or ACEA-1021, but potentiated the effects of dizocilpine, memantine, and eliprodil. Based on the present results, one can suggest that the repeated administration of a competitive NMDA receptor antagonist differentially affects the functional activity of various sites on NMDA receptor complex.
机译：关于NMDA受体拮抗剂的临床使用的当前观点推断出重复给药方案用于不同病理状态的治疗。不同NMDA受体拮抗剂之间耐受性和交叉耐受性的发展可能是有助于这些药物临床疗效的重要因素。本研究旨在表征对多种位点选择性NMDA受体拮抗剂产生操作反应减量的能力的耐受性和交叉耐受性的发展（多次消灭9 s固定间隔1-s的水强化时间表）。急性给予D-CPPen（SDZ EAA 494; 1-5.6 mg / kg），地佐西平（MK-801; 0.03-0.3 mg / kg），美金刚（0.3-17 mg / kg），ACEA-1021（10-56毫克/公斤）和依洛地尔（1-30毫克/公斤）差异影响手术反应。观察到响应率的增加和减少以及响应的准确性。重复暴露于D-CPPen（5.6 mg / kg，每天一次，连续7天）可减轻D-CPPen或ACEA-1021急性攻击所产生的行为破坏，但增强了地佐西平，美金刚和依洛地尔的作用。根据目前的结果，可以提出重复施用竞争性NMDA受体拮抗剂有区别地影响NMDA受体复合物上各个位点的功能活性。

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