DIFFERENTIAL BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF COMPETITIVE AND NONCOMPETITIVE NMDA RECEPTOR ANTAGONISTS IN RATS
DIFFERENTIAL BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF COMPETITIVE AND NONCOMPETITIVE NMDA RECEPTOR ANTAGONISTS IN RATS
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DOI：
10.1016/0014-2999(92)90288-f
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发表时间：
1992-12-08
影响因子：
5
通讯作者：
SCHMIDT, WJ
中科院分区：
文献类型：
--
作者：
BUBSER, M;KESEBERG, U;SCHMIDT, WJ
在大鼠中研究了非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂地佐环平和美金刚以及竞争性NMDA受体拮抗剂CGP 39551的行为和生化效应。全身注射地佐环平（0.33毫克/公斤）增加运动和饲养在一个开放的领域，而美金刚（20毫克/公斤）只增加自发活动。CGP 39551（10和20 mg/kg）未改变旷场活动。多巴胺（DA）代谢--通过二羟苯乙酸/多巴胺（DOPAC/DA）的比值来衡量--在前额皮质和丘脑核中对地佐环平的反应中增加。美金刚胺增强DOPAC/DA在前额皮质，脑桥核，并在较低程度上在后纹状体。与非竞争性NMDA受体拮抗剂相比，CGP 39551并没有增加皮质下结构的DA代谢，甚至降低了前额叶皮质的DOPAC/ DA。这些结果表明，竞争性和非竞争性NMDA受体拮抗剂影响大鼠自发运动的差异。生化数据表明，非竞争性NMDA受体拮抗剂的兴奋作用至少部分是由于多巴胺能系统的激活。这两种类型的NMDA受体拮抗剂的差异影响所涉及的潜在机制进行了讨论。
The behavioural and biochemical effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine and memantine, and the competitive NMDA receptor antagonist, CGP 39551, were investigated in rats. Systemic injections of dizocilpine (0.33 mg/kg) increased locomotion and rearing in an open field, whereas memantine (20 mg/kg) increased only locomotor activity. CGP 39551 (10 and 20 mg/kg) did not change open field activity. Dopamine (DA) metabolism - as measured by the ratio of dihydroxyphenylacetic acid/dopamine (DOPAC/DA) - increased in response to dizocilpine in the prefrontal cortex and the nucleus accumbens. Memantine enhanced DOPAC/DA in the prefrontal cortex, the nucleus accumbens and to a lesser degree in the posterior striatum. In contrast to non-competitive NMDA receptor antagonists, CGP 39551 did not increase DA metabolism of subcortical structures and even decreased DOPAC/ DA in the prefrontal cortex. These results indicate that competitive and non-competitive NMDA receptor antagonists affect spontaneous locomotion differentially in rats. The biochemical data imply that the stimulant actions of non-competitive NMDA receptor antagonists are at least partially due to activation of ascending dopaminergic systems. Potential mechanisms involved in the differential effects of both types of NMDA receptor antagonists are discussed.