Damianopoulos E N, Carey R J
SUNY Health Science Center, Syracuse, USA.
Behav Brain Res. 1995 Jun;68(2):219-28. doi: 10.1016/0166-4328(94)00175-f.
The role of the N-methyl-D-aspartate (NMDA) receptors in cocaine conditioning and sensitization of locomotor activity was studied in four groups of Sprague-Dawley rats. A sub-motoric dose of the NMDA antagonist MK-801 (0.1 mg/kg, i.p.) was employed using a novel dual-compartment Pavlovian drug conditioning paradigm. The animals were placed sequentially in two different test environments in which locomotor activity was monitored. In the first compartment, the animals always received a non-drug test for 20 min. Upon completion of this test, the animals received either saline, cocaine (10 mg/kg i.p.), MK-801 or MK-801 plus cocaine depending on group assignment and were then placed immediately into the second compartment and again tested for 20 min. A total of six non-drug and six drug tests were conducted every other day over a 12-day period. Across all drug/saline treatment and post-treatment tests for conditioning, there were no statistical differences in locomotor activity among the saline and drug treatment groups in the non-drug test environment. In the drug/saline associated environment, however, cocaine had a reliable stimulant effect on locomotion when administered alone or in combination with MK-801. Following a 1-day and again after 21-days of withdrawal, all animals were administered a non-drug test for conditioning in which no injections were administered. On both tests, all groups had equivalent activity levels in the non-drug environment. In the drug/saline environment, only the cocaine group of the three drug treatment groups exhibited conditioned hyperlocomotion. Importantly, MK-801 blocked conditioned hyperlocomotion in the combined cocaine+MK-801 group. MK-801 did not alter serum or brain cocaine concentration or the cocaine effects on dopamine metabolism in limbic brain tissue. The co-administration of MK-801 with cocaine, however, blocked the corticosterone release effect of cocaine. Thus, the NMDA receptor site appears critical for cocaine induced conditioning and for corticosterone release.
在四组斯普拉格-道利大鼠中研究了N-甲基-D-天冬氨酸（NMDA）受体在可卡因条件反射及运动活动敏化中的作用。采用一种新型双室巴甫洛夫式药物条件反射范式，使用亚运动剂量的NMDA拮抗剂MK-801（0.1毫克/千克，腹腔注射）。将动物依次置于两个不同的测试环境中，监测其运动活动。在第一个隔室中，动物总是接受20分钟的非药物测试。该测试完成后，根据分组，动物接受生理盐水、可卡因（10毫克/千克腹腔注射）、MK-801或MK-801加可卡因，然后立即放入第二个隔室，再次测试20分钟。在12天的时间里，每隔一天总共进行六次非药物测试和六次药物测试。在所有药物/生理盐水处理及条件反射的处理后测试中，在非药物测试环境下，生理盐水组和药物处理组之间的运动活动没有统计学差异。然而，在药物/生理盐水相关环境中，可卡因单独给药或与MK-801联合给药时，对运动有可靠的刺激作用。在停药1天及21天后，对所有动物进行一次不注射药物的条件反射非药物测试。在这两次测试中，所有组在非药物环境中的活动水平相当。在药物/生理盐水环境中，三个药物处理组中只有可卡因组表现出条件性运动亢进。重要的是，MK-801在可卡因+MK-801联合组中阻断了条件性运动亢进。MK-801不会改变血清或脑内可卡因浓度，也不会改变可卡因对边缘脑组织中多巴胺代谢的影响。然而，MK-801与可卡因联合给药时，会阻断可卡因的皮质酮释放作用。因此，NMDA受体位点似乎对可卡因诱导的条件反射及皮质酮释放至关重要。
