Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Laboratório de Álcool e Tabaco (LAT), Universidade Federal do Rio Grande do Sul - UFRGS, Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil.
Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Sarmento Leite, 245, 90050-170, Porto Alegre, RS, Brazil.
Alcohol. 2020 Feb;82:63-70. doi: 10.1016/j.alcohol.2019.08.005. Epub 2019 Aug 29.
Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This imbalance includes changes in GABA receptors - importantly in GABA subtypes - and glutamate receptors, especially in NMDA subtypes. A better comprehension of the different roles of GABAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2 × /day, for 28 days. From day 29 to day 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally (i.p.), once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A, was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.
慢性饮酒及其戒断会破坏 GABA 能和谷氨酸能系统之间的微妙平衡。这种失衡包括 GABA 受体的变化——尤其是 GABA 亚型——和谷氨酸受体，特别是 NMDA 亚型。更好地理解 GABAAR 和 NMDAR 亚基的不同作用，有助于确定新的策略来对抗酒精戒断期间观察到的有害影响。牛磺酸是一种磺基氨基酸，因其具有神经调节特性，被提议减轻酒精戒断症状。在这项研究中，我们评估了慢性酒精处理或酒精戒断大鼠海马中的 GABAAR 和 NMDAR 亚基之间的相关性，以及牛磺酸处理对这些参数的影响。雄性 Wistar 大鼠通过口服灌胃接受酒精（2 g/kg）或水（对照），每天 2 次，共 28 天。从第 29 天到第 33 天，戒断大鼠接受水而不是酒精，所有组都重新分配接受 100 mg/kg 牛磺酸或生理盐水腹膜内（i.p.）注射，每天一次。第 34 天，大鼠被安乐死，海马被解剖用于通过 RT-qPCR 测定 GABAAR α1、α4、δ 和 γ2 以及 NMDAR GluN2A 和 GluN2B 亚基 mRNA 表达。在研究的 GABAAR 和 NMDA 亚基中，各组之间没有差异。然而，我们观察到牛磺酸诱导的 α1 和 γ2 亚基之间的相关性，而在酒精组中观察到 α4 和 GluN2A 之间的相关性。在接受酒精和牛磺酸治疗的组中，我们观察到 α1 和 GluN2A 之间的额外相关性。戒断 5 天后，在对照组中观察到 δ 和 GluN2A 之间的相关性得到恢复。亚基之间的相关性表明戒断大鼠的 GABA 能和谷氨酸能系统发生了神经适应。这项研究的结果有助于阐明酒精使用和戒断期间观察到的神经适应背后的机制。
