College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Institute of Forensic Injury, Institute of Forensic Bioevidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, People's Republic of China.
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, People's Republic of China; Institute of Forensic Injury, Institute of Forensic Bioevidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, People's Republic of China; Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China.
Neurosci Lett. 2023 Jan 1;792:136952. doi: 10.1016/j.neulet.2022.136952. Epub 2022 Nov 4.
Drug addiction, including methamphetamine (METH) addiction, is a significant public health and social issue. Perturbations in intracellular Ca homeostasis are associated with drug addiction. K-dependent Na/Ca exchanger 2 (NCKX2) is located on neuronal cell membranes and constitutes a Ca clearance mechanism, with key roles in synaptic plasticity. NCKX2 is associated with motor learning, memory, and cognitive functions. However, the role of NCKX2 in METH addiction remains unclear. In this study, we investigated the expression levels of NCKX2 in four addiction-related brain regions: the prefrontal cortex (PFc), nucleus accumbens (NAc), dorsal striatum (DS), and hippocampus (Hip) in a C57/BL6 mouse model of METH-induced conditioned place preference (CPP) and behavioral sensitization. Levels of NCKX2 were unchanged in these brain regions in mice with METH-induced CPP but were decreased in the PFc and NAc of mice with METH-induced behavioral sensitization. Adeno-associated virus (AAV)-mediated overexpression of NCKX2 in the PFc attenuated the expression phase of METH-induced behavioral sensitization in mice, whereas AAV-mediated knockdown of NCKX2 enhanced the effects of METH. Collectively, our results suggest that NCKX2 is involved in METH-induced behavioral sensitization but does not affect conditioned reward-related memory, highlighting the potential of NCKX2 as a molecular target for studying the mechanisms underscoring METH addiction.
药物成瘾，包括冰毒（METH）成瘾，是一个重大的公共卫生和社会问题。细胞内 Ca2+ 稳态的紊乱与药物成瘾有关。K 依赖性 Na+/Ca2+ 交换体 2（NCKX2）位于神经元细胞膜上，构成 Ca2+ 清除机制，在突触可塑性中起关键作用。NCKX2 与运动学习、记忆和认知功能有关。然而，NCKX2 在 METH 成瘾中的作用尚不清楚。在这项研究中，我们研究了 NCKX2 在四个与成瘾相关的脑区（前额叶皮层（PFc）、伏隔核（NAc）、背侧纹状体（DS）和海马（Hip））中的表达水平，在 METH 诱导的条件性位置偏好（CPP）和行为敏化的 C57/BL6 小鼠模型中。METH 诱导 CPP 小鼠这些脑区的 NCKX2 水平不变，但 METH 诱导行为敏化小鼠的 PFc 和 NAc 中 NCKX2 水平降低。PFc 中腺相关病毒（AAV）介导的 NCKX2 过表达减弱了 METH 诱导行为敏化的表达阶段，而 AAV 介导的 NCKX2 敲低增强了 METH 的作用。总的来说，我们的结果表明 NCKX2 参与了 METH 诱导的行为敏化，但不影响条件性奖励相关记忆，这突出了 NCKX2 作为研究 METH 成瘾机制的分子靶点的潜力。
