Kuriyama K, Ohkuma S, Taguchi J, Hashimoto T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Physiol Behav. 1987;40(3):393-9. doi: 10.1016/0031-9384(87)90067-9.
Effects of alcohol (ethanol) and acetaldehyde on the metabolism and function of primary cultured GABAergic neurons and that of salsolinol, a condensation product of acetaldehyde with dopamine, on cerebral GABA/benzodiazepine (BZP) receptor complex were investigated. In vitro addition of acetaldehyde induced a significant reduction not only on the content of GABA but also on the basal and GABA-activated [3H]flunitrazepam ([3H]FLN) bindings in primary cultured neurons. In contrast, alcohol exhibited only suppressive effects on [3H]FLN binding as well as on the enhancement of [3H]FLN binding by GABA. On the other hand, salsolinol showed a significant stimulatory effect on [3H]FLN binding to cerebral particulate fractions obtained from alcohol-untreated mice in the presence of NaCl. Although a similar activation of cerebral [3H]FLN binding by salsolinol was found in alcohol-treated mice, this activation was significantly weaker in alcohol-withdrawn mice than those found in alcohol-untreated as well as alcohol-inhaled mice. These results strongly suggest that acetaldehyde may have more important pathophysiological roles than those of alcohol in the exhibition of neurotoxicity during alcohol intake. The present results also suggest that salsolinol may have a modulatory role on cerebral benzodiazepine receptor and the decreased capacity of such a modulating mechanism may be involved in the exhibition of alcohol withdrawal syndrome, possibly by decreasing the function of endogenous ligands for benzodiazepine receptor in the brain.
研究了酒精（乙醇）和乙醛对原代培养的γ-氨基丁酸能神经元的代谢和功能的影响，以及乙醛与多巴胺的缩合产物萨索林对脑γ-氨基丁酸/苯二氮䓬（BZP）受体复合物的影响。体外添加乙醛不仅导致原代培养神经元中γ-氨基丁酸含量显著降低，还导致基础和γ-氨基丁酸激活的[³H]氟硝西泮（[³H]FLN）结合显著减少。相比之下，酒精仅对[³H]FLN结合以及γ-氨基丁酸对[³H]FLN结合的增强具有抑制作用。另一方面，在存在氯化钠的情况下，萨索林对从未经酒精处理的小鼠获得的脑微粒体部分的[³H]FLN结合显示出显著的刺激作用。尽管在经酒精处理的小鼠中也发现了萨索林对脑[³H]FLN结合的类似激活，但在戒酒后的小鼠中，这种激活明显弱于未经酒精处理以及吸入酒精的小鼠。这些结果强烈表明，在酒精摄入期间神经毒性的表现中，乙醛可能比酒精具有更重要的病理生理作用。目前的结果还表明，萨索林可能对脑苯二氮䓬受体具有调节作用，这种调节机制能力的降低可能参与了酒精戒断综合征的表现，可能是通过降低脑内苯二氮䓬受体内源性配体的功能。
