Department of Microbiology, Karaj Branch Islamic Azad University, Karaj, Iran.
Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cent Nerv Syst Agents Med Chem. 2023;23(2):119-125. doi: 10.2174/1871524923666230816103223.
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.
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.
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.
We concluded that the NMDA receptor in the PVT nucleus changes the development of Mor dependence.
NMDA 受体在阿片类药物身体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）中的神经元兴奋性。目前的研究旨在探讨通过在 PVT 核内给予 MK801 阻断 NMDA 受体是否会影响吗啡（Mor）依赖的发展，从而影响吗啡戒断后大鼠的行为指标。
使用体重为 250-300g 的雄性 Wistar 大鼠。为了诱导药物依赖，我们以 24 小时的间隔皮下（s.c.）注射 Mor（6、16、26、36、46、56 和 66mg/kg，2ml/kg），共 7 天。动物被分为两组，在给予 Mor 之前的 7 天内，NMDA 受体拮抗剂 MK801（20mM，0.1ml）或其载体被应用于 PVT 核内。在第 8 天，在注射纳洛酮（Nal，2.5mg/kg，ip）后，检查 25 分钟的戒断行为。
目前的结果表明，PVT 核内 NMDA 受体的阻断显著增加了吗啡依赖（Mor-d）大鼠应用 Nal 后引发的戒断行为。
我们得出结论，PVT 核内的 NMDA 受体改变了 Mor 依赖的发展。
