Abstract：
The present study aimed to investigate the role of agmatine in the neurobiology underlying memory impairment during ethanol withdrawal in rats. Sprague-Dawley rats were subjected to a 21-day chronic ethanol exposure regimen (2.4 % w/v ethanol for 3 days, 4.8 % w/v for the next 4 days, and 7.2 % w/v for the following 14 days), followed by a withdrawal period. Memory impairment was assessed using the passive avoidance test (PAT) at 24, 48, and 72 h post-withdrawal. The ethanol-withdrawn rats displayed a significant decrease in step-through latency in the PAT, indicative of memory impairment at 72 h post-withdrawal. However, administration of agmatine (40 µg/rat) and its modulators (L-arginine, arcaine, and amino-guanidine) significantly increases the latency time in the ethanol-withdrawn rats, demonstrating the attenuation of memory impairment. Further, pretreatment with imidazoline receptor agonists enhances agmatine\'s effects, while antagonists block them, implicating imidazoline receptors in agmatine\'s actions. Neurochemical analysis in ethanol-withdrawn rats reveals dysregulated glutamate and GABA levels, which was attenuated by agmatine and its modulators. By examining the effects of agmatine administration and modulators of endogenous agmatine, the study aimed to shed light on the potential therapeutic implications of agmatinergic signaling in alcohol addiction and related cognitive deficits. Thus, the present findings suggest that agmatine administration and modulation of endogenous agmatine levels hold potential as therapeutic strategies for managing alcohol addiction and associated cognitive deficits. Understanding the neurobiology underlying these effects paves the way for the development of novel interventions targeting agmatinergic signaling in addiction treatment.
摘要：
本研究旨在探讨胍丁胺在大鼠乙醇戒断过程中记忆障碍的神经生物学中的作用。Sprague-Dawley大鼠接受21天的慢性乙醇暴露方案（2.4％w/v乙醇3天，未来4天为4.8%w/v，在接下来的14天内为7.2%w/v)，其次是退出期。在戒断后24、48和72小时使用被动回避测试（PAT）评估记忆障碍。戒除乙醇的大鼠在PAT中显示出步进潜伏期的显着减少，戒断后72小时的记忆障碍。然而,给药胍丁胺（40ug/大鼠）及其调节剂（L-精氨酸，arcaine,和氨基胍）显着增加了戒除乙醇的大鼠的潜伏期时间，证明记忆障碍的衰减。Further,用咪唑啉受体激动剂预处理可增强胍丁胺的作用，当拮抗剂阻止它们时，咪唑啉受体参与胍丁胺的作用。乙醇戒断大鼠的神经化学分析显示谷氨酸和GABA水平失调，通过胍丁胺及其调节剂减弱。通过检查胍丁胺给药和内源性胍丁胺调节剂的作用，该研究旨在阐明在酒精成瘾和相关认知缺陷中，肌醇敏能信号的潜在治疗意义。因此，本研究结果表明,胍丁胺的给药和内源性胍丁胺水平的调节有可能作为控制酒精成瘾和相关认知缺陷的治疗策略.了解这些作用背后的神经生物学为开发针对成瘾治疗中的激素能信号的新型干预措施铺平了道路。
