NMDA Receptors in the Rat Paraventricular Thalamic Nucleus Reduce the Naloxone-induced Morphine Withdrawal.

Q3 Psychology Central nervous system agents in medicinal chemistry Pub Date : 2023-01-01 DOI:10.2174/1871524923666230816103223

Fatemeh Babaei, Masoumeh Kourosh-Arami, Mona Farhadi

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Abstract

Background: NMDA receptors have a significant role in the development of opioid physical dependence. Evidence demonstrated that a drug of abuse enhances neuronal excitability in the Paraventricular Nucleus (PVT). The current research studied whether blocking NMDA receptors through the administration of MK801 in the PVT nucleus could affect the development of Morphine (Mor) dependence and hence the behavioral indices induced by morphine withdrawal in rats.

Methods: Male Wistar rats weighing 250-300 g were used. For induction of drug dependence, we injected Mor subcutaneously (s.c.) (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 hours for 7 days. Animals were divided into two groups in which the NMDA receptor antagonist, MK801 (20 mM in 0.1 ml), or its vehicle were applied into the PVT nucleus for 7 days before each Mor administration. On day 8, after injection of naloxone (Nal, 2.5 mg/kg, i.p.), withdrawal behaviors were checked for 25 min.

Results: The current results demonstrated that the blockade of the NMDA receptor in the PVT nucleus significantly increased withdrawal behaviors provoked by the application of Nal in morphinedependent (Mor-d) rats.

Conclusion: We concluded that the NMDA receptor in the PVT nucleus changes the development of Mor dependence.

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大鼠室旁丘脑核NMDA受体减少纳洛酮诱导的吗啡戒断。

背景：NMDA受体在阿片类物质依赖的发展中起着重要作用。有证据表明，滥用药物会增强室旁核（PVT）的神经元兴奋性。目前的研究通过在PVT核中给予MK801阻断NMDA受体是否会影响吗啡依赖的发展，从而影响吗啡戒断诱导的大鼠行为指标。方法：雄性Wistar大鼠，体重250～300g。为了诱导药物依赖性，我们以24小时的间隔皮下注射Mor（皮下注射）（6、16、26、36、46、56和66mg/kg，2ml/kg），持续7天。将动物分为两组，其中NMDA受体拮抗剂MK801（20mM，0.1ml）或其载体在每次Mor给药前应用于PVT核7天。在第8天，在注射纳洛酮（Nal，2.5 mg/kg，i.p.）后，检查25分钟的戒断行为。结果：目前的结果表明，阻断PVT核中的NMDA受体显著增加了吗啡依赖性（Mor-d）大鼠应用Nal引起的戒断行为。结论：PVT核NMDA受体改变了Mor依赖性的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology

CiteScore

2.10

自引率

0.00%

发文量

期刊介绍： Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.