Peregud D I, Vorontsova O N, Yakovlev A A, Panchenko L F, Gulyaeva N V
Federal State National Scientific Center of Drug Addiction, Russian Ministry of Health, 3 Malyi Mogol'tsevskii Lane, Moscow, Russia.
Neurosci Behav Physiol. 2008 Jun;38(5):443-8. doi: 10.1007/s11055-008-9000-y. Epub 2008 Jul 8.
Opiate dependence results from impairments of neuronal plasticity, i.e., so-called aberrant neuroplasticity, formation of which involves long-term structural-functional rearrangements persisting even during drug abstinence. Nitric oxide (NO) is involved both in mediating the effects of opiates and in the mechanisms of some types of neuroplasticity, so NO may potentially take part in the development of psychopathological processes on opiate withdrawal. The present study addressed measures of the nitrergic system (nitric oxide synthase (NOS) activity and nitrite and nitrate (NO (x) (-) ) concentrations) in areas of the rat brain; anxiety was also assessed, in terms of behavioral measures in the elevated plus maze, during morphine withdrawal. NOS activity was found to increase by day 3, while the NO (x) (-) concentration was increased by day 6 of withdrawal, these changes being seen only in the hippocampus. At six days after morphine withdrawal, rats showed more entries into the open arms of the elevated plus maze and remained in these arms longer. Correlations were found between measures of the NO system in the hippocampus and the behavior of the animals in the maze. These results suggest that changes in the activity of the nitrergic system in the hippocampus represent one of the molecular mechanisms impairing the behavior of animals in abstinence.
阿片类药物依赖源于神经元可塑性受损，即所谓的异常神经可塑性，其形成涉及长期的结构 - 功能重排，甚至在药物戒断期间仍持续存在。一氧化氮（NO）既参与介导阿片类药物的作用，也参与某些类型神经可塑性的机制，因此NO可能潜在地参与阿片类药物戒断时精神病理过程的发展。本研究探讨了大鼠脑区中氮能系统的指标（一氧化氮合酶（NOS）活性以及亚硝酸盐和硝酸盐（NO(x)(-)）浓度）；在吗啡戒断期间，还通过高架十字迷宫中的行为指标评估了焦虑情况。发现NOS活性在戒断第3天增加，而NO(x)(-)浓度在戒断第6天增加，这些变化仅在海马体中观察到。吗啡戒断6天后，大鼠进入高架十字迷宫开放臂的次数更多，并且在这些臂中停留的时间更长。在海马体中NO系统的指标与动物在迷宫中的行为之间发现了相关性。这些结果表明，海马体中氮能系统活性的变化代表了一种损害动物戒断行为的分子机制。
