Dehkordi Ozra, Lin Stephen, Mohamud Safia F, Millis Richard M, Wang Paul
Neurology, Howard University College of Medicine, Washington, USA.
Radiology, Howard University College of Medicine, Washington, USA.
Cureus. 2025 Mar 3;17(3):e79972. doi: 10.7759/cureus.79972. eCollection 2025 Mar.
It is well known that opiate addiction is a neurobiological disease associated with dysregulation of multiple neurotransmitters and neurochemicals. Previous H nuclear magnetic resonance (NMR) studies have yielded mixed findings concerning opiate-induced neurometabolic changes at key reward-addiction sites. Whether such changes reflect the conditions in a live animal remains unknown. The present study was therefore designed to fill this knowledge gap by determining the effects of morphine-induced neurometabolic changes under in-vivo conditions.
In-vivo H NMR spectroscopy (SA Instruments, Stony Brook, NY) was used to measure neurochemical changes in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of mice, subjected to twice-daily injections of morphine (10 mg kg s.c.) for five days.
Morphine induced significant changes in the concentrations of a number of metabolites in both mPFC and NAc. The glutamine component of the glutamine-glutamate-GABA excitatory-inhibitory cycle, increased in both mPFC and NAc. Significant increase in glutamate was also observed at mPFC, but not in NAc. The phosphocreatine, marker for energy metabolism, and the N-acetylaspartate marker for neuronal viability and energy metabolism decreased significantly in both mPFC and NAc. Glycerophosphocholine + phosphocholine, markers for cell membrane integrity, increased significantly in both NAc and mPFC after morphine. The antioxidant neurometabolites taurine and glutathione increased significantly in NAc; however, taurine decreased, and glutathione was unchanged in mPFC after morphine. Inositol, a marker for neuroinflammation, increased significantly in NAc.
The present study is the first in-vivo H NMR spectroscopy in mice to demonstrate morphine-induced dysregulation of multiple metabolites and neurochemicals within the reward-addiction neurocircuitry.
众所周知，阿片类药物成瘾是一种与多种神经递质和神经化学物质失调相关的神经生物学疾病。先前的氢核磁共振（NMR）研究在阿片类药物引起的关键奖赏 - 成瘾部位神经代谢变化方面得出了不一致的结果。这些变化是否反映了活体动物的状况仍不清楚。因此，本研究旨在通过确定吗啡在体内条件下引起的神经代谢变化来填补这一知识空白。
使用体内氢核磁共振波谱法（SA Instruments，纽约州斯托尼布鲁克）测量小鼠伏隔核（NAc）和内侧前额叶皮质（mPFC）的神经化学变化，小鼠每天皮下注射两次吗啡（10 mg/kg），持续五天。
吗啡引起mPFC和NAc中多种代谢物浓度的显著变化。谷氨酰胺 - 谷氨酸 - GABA兴奋性 - 抑制性循环中的谷氨酰胺成分在mPFC和NAc中均增加。在mPFC中也观察到谷氨酸显著增加，但在NAc中未观察到。能量代谢标志物磷酸肌酸以及神经元活力和能量代谢标志物N - 乙酰天门冬氨酸在mPFC和NAc中均显著降低。甘油磷酸胆碱 + 磷酸胆碱，细胞膜完整性标志物，在吗啡作用后在NAc和mPFC中均显著增加。抗氧化神经代谢物牛磺酸和谷胱甘肽在NAc中显著增加；然而，吗啡作用后mPFC中的牛磺酸减少，谷胱甘肽无变化。肌醇，神经炎症标志物，在NAc中显著增加。
本研究是首次在小鼠体内进行的氢核磁共振波谱研究，证明吗啡诱导奖赏 - 成瘾神经回路内多种代谢物和神经化学物质的失调。
