一氧化氮对吗啡诱导的失忆的影响以及与多巴胺能受体药物的相互作用。

Influence of nitric oxide on morphine-induced amnesia and interactions with dopaminergic receptor agents.

作者信息

Rezayof Ameneh, Amini Rana, Rassouli Yassaman, Zarrindast Mohammad-Reza

机构信息

School of Biology, University College of Science, University of Tehran, Tehran, Iran.

出版信息

Physiol Behav. 2006 Jun 15;88(1-2):124-31. doi: 10.1016/j.physbeh.2006.03.017. Epub 2006 Apr 21.

Abstract

The interactions of dopaminergic receptors and nitric oxide (NO) with morphine-induced memory of passive avoidance have been investigated in mice. Pre-training administration of morphine (1, 3 and 5 mg/kg, s.c.) dose-dependently decreased the learning of a one-trial passive avoidance task. Pre-training administration of L-arginine, a nitric oxide precursor (50, 100 and 200 mg/kg, i.p.), alone did not affect memory formation. The drug (100 and 200 mg/kg) decreased significantly amnesia induced by pre-training morphine (5 mg/kg). Pre-training administration of L-NAME (N(G)-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (20 and 30 mg/kg, i.p.), dose-dependently impaired memory formation. In addition, co-pretreatment of different doses of L-NAME (10, 20 and 30 mg/kg) with lower dose of morphine (1 mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Pre-training administration of apomorphine, a dopaminergic receptor agonist (0.25, 0.5 and 1 mg/kg, i.p.), alone also did not affect memory formation, but morphine-induced amnesia was significantly inhibited by pretreatment with apomorphine (0.5 and 1 mg/kg, 5 min, i.p.). On the other hand, the inhibition of morphine-induced amnesia by L-arginine (200 mg/kg, i.p.) was significantly decreased by pretreatment with different doses of dopamine D1 receptor antagonist, SCH 23390 (0.001, 0.01 and 0.1 mg/kg, i.p.) or D2 receptor antagonist, sulpiride (12.5, 25, 50 and 100 mg/kg, i.p.). However, the dopamine receptor antagonists could not affect memory formation by themselves. It may be concluded that the morphine-induced impairment of memory formation can be prevented by nitric oxide donor and, in this effect, dopaminergic mechanism is involved.

摘要

在小鼠中研究了多巴胺能受体和一氧化氮(NO)与吗啡诱导的被动回避记忆之间的相互作用。吗啡(1、3和5毫克/千克,皮下注射)预训练给药剂量依赖性地降低了单次被动回避任务的学习能力。一氧化氮前体L-精氨酸(50、100和200毫克/千克,腹腔注射)单独预训练给药不影响记忆形成。该药物(100和200毫克/千克)显著减轻了预训练吗啡(5毫克/千克)诱导的失忆。一氧化氮合酶(NOS)抑制剂L-NAME(N(G)-硝基-L-精氨酸甲酯,20和30毫克/千克,腹腔注射)预训练给药剂量依赖性地损害记忆形成。此外,不同剂量的L-NAME(10、20和30毫克/千克)与较低剂量的吗啡(1毫克/千克)共同预处理,后者本身不会诱导失忆,但会导致记忆形成受到抑制。多巴胺能受体激动剂阿扑吗啡(0.25、0.5和1毫克/千克,腹腔注射)单独预训练给药也不影响记忆形成,但阿扑吗啡(0.5和1毫克/千克,腹腔注射,5分钟)预处理可显著抑制吗啡诱导的失忆。另一方面,不同剂量的多巴胺D1受体拮抗剂SCH 23390(0.001、0.01和0.1毫克/千克,腹腔注射)或D2受体拮抗剂舒必利(12.5、25、50和100毫克/千克,腹腔注射)预处理可显著降低L-精氨酸(200毫克/千克,腹腔注射)对吗啡诱导失忆的抑制作用。然而,多巴胺受体拮抗剂自身不会影响记忆形成。可以得出结论,一氧化氮供体可以预防吗啡诱导的记忆形成损害,并且在这种作用中涉及多巴胺能机制。

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