Biomedical Engineering Department, University of Houston, 3517 Cullen Blvd, Houston, TX 77204, USA.
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Int J Mol Sci. 2023 Nov 14;24(22):16303. doi: 10.3390/ijms242216303.
Dopamine (DA)'s relationship with addiction is complex, and the related pathways in the mesocorticolimbic system are used to deliver DA, regulating both behavioral and perceptual actions. Specifically, the mesolimbic pathway connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial in regulating memory, emotion, motivation, and behavior due to its responsibility to modulate dopamine. To better investigate the relationship between DA and addiction, more advanced mapping methods are necessary to monitor its production and propagation accurately and efficiently. In this study, we incorporate dLight1.2 adeno-associated virus (AAV) into our latest CMOS (complementary metal-oxide semiconductor) imaging platform to investigate the effects of two pharmacological substances, morphine and cocaine, in the NAc using adult mice. By implanting our self-fabricated CMOS imaging device into the deep brain, fluorescence imaging of the NAc using the dLight1.2 AAV allows for the visualization of DA molecules delivered from the VTA in real time. Our results suggest that changes in extracellular DA can be observed with this adapted system, showing potential for new applications and methods for approaching addiction studies. Additionally, we can identify the unique characteristic trend of DA release for both morphine and cocaine, further validating the underlying biochemical mechanisms used to modulate dopaminergic activation.
多巴胺(DA)与成瘾的关系很复杂,中脑边缘多巴胺系统中的相关通路用于传递 DA,调节行为和感知活动。具体来说,连接腹侧被盖区(VTA)和伏隔核(NAc)的中脑边缘通路在调节记忆、情绪、动机和行为方面至关重要,因为它负责调节多巴胺。为了更好地研究 DA 与成瘾之间的关系,需要更先进的映射方法来准确高效地监测其产生和传播。在这项研究中,我们将 dLight1.2 腺相关病毒(AAV)纳入我们最新的 CMOS(互补金属氧化物半导体)成像平台,以研究成年小鼠 NAc 中两种药理学物质吗啡和可卡因的作用。通过将我们自制的 CMOS 成像设备植入大脑深部,使用 dLight1.2 AAV 对 NAc 进行荧光成像,可以实时可视化来自 VTA 的 DA 分子的传递。我们的结果表明,通过这种适应性系统可以观察到细胞外 DA 的变化,为成瘾研究提供了新的应用和方法的潜力。此外,我们可以识别出吗啡和可卡因释放 DA 的独特特征趋势,进一步验证了用于调节多巴胺能激活的潜在生化机制。