L-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine.

L-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine.
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L-NAME 和 MK-801 减弱对可卡因运动刺激作用的敏感性。

DOI:
10.1016/0024-3205(93)90559-l
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发表时间:
1993
期刊:
影响因子:
6.1
通讯作者:
Bozarth,MA
Bozarth,MA
中科院分区:
医学2区
文献类型:
--
作者:
Pudiak,CM;Bozarth,MA

文献摘要

被引文献

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在连续21天注射可卡因后,每天测试运动活性。受试者在测试前30分钟接受生理盐水、一氧化氮合酶抑制剂Nω-硝基-L-精氨酸(L-NAME)或NMDA受体拮抗剂MK-801预处理。其他大鼠在测试前每天注射生理盐水而不是可卡因。用生理盐水预处理并每天注射可卡因的大鼠在21天的测试期内表现出运动活性增加。L-NAME预处理抑制可卡因刺激的自发活动,而MK-801预处理增加自发活动。为了测试对可卡因的行为敏感性,大鼠在最后一次每日注射后72小时注射可卡因。与每日仅注射生理盐水的受试者相比,每日注射可卡因的生理盐水预处理受试者中观察到致敏作用,但L-NAME和MK-801预处理均强烈减弱可卡因致敏作用。这一发现与一氧化氮和NMDA受体在细胞适应和学习中的作用一致。
Locomotor activity was tested daily following cocaine injections across 21 consecutive days. Subjects were pretreated 30-min before testing with physiological saline, the nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NAME), or the NMDA-receptor antagonist MK-801. Other rats received daily injections of physiological saline instead of cocaine just prior to testing. Rats pretreated with saline and injected daily with cocaine showed increased locomotor activity across the 21-day test period. L-NAME pretreatment depressed cocaine-stimulated locomotor activity, while MK-801 pretreatment increased locomotor activity. To test for behavioral sensitization to cocaine, rats were injected with cocaine 72 hours after their last daily injections. Sensitization was seen in saline pretreated subjects injected daily with cocaine compared to subjects injected daily with saline only, but both L-NAME and MK-801 pretreatment strongly attenuated cocaine sensitization. This finding is consistent with the proposed roles of nitric oxide and NMDA-receptors in cellular adaptation and learning.