Korpi E R, Tuominen K, Uusi-Oukari M, Saransaari P, Oja S S, Suzdak P D
Research Laboratories, Alko Ltd, Helsinki, Finland.
Ann Med. 1990;22(4):253-8. doi: 10.3109/07853899009148936.
In this paper we describe new data and review some studies on the mechanisms of alcohol-induced motor impairment in rats. Habituation to handling did not affect the naive behavioural differences between the alcohol sensitive and alcohol insensitive rat lines. Nor was there any effect on the differential sensitivities of the lines to the motor impairing and hypnotic effects of alcohol. Peripheral mechanisms may be involved in the differential behaviours of these lines, as the plasma corticosterone response was much weaker in the alcohol sensitive animals, suggesting a limited capacity to react to stress and alcohol. A similar blunted response to acute ethanol exposure was found in the uptake of the benzodiazepine antagonist [3H]Ro 15-1788 in vivo by the cerebellum of alcohol sensitive rats. The finding that these rat lines do not have any general differences in their brain inhibitory GABAergic receptors was extended to the spinal cord inhibitory glycinergic receptors, which showed only a modest line difference in their dissociation constant. The apparent localisation of the two main receptor differences (high-affinity [3H]muscimol binding and diazepam sensitivity of [3H]Ro 15-4513 binding) to the cerebellar granule layer suggests a genetic modification in the granule cells of alcohol-sensitive rats. In conclusion, our studies on acute intoxication by moderate alcohol doses show that several central nervous and peripheral factors may be involved in this behaviour. As many of these factors mitigate the effects of alcohol, alcohol antagonistic treatments should be aimed at activating and supporting multiple adaptive phenomena.
在本文中，我们描述了新的数据，并回顾了一些关于酒精诱导大鼠运动功能障碍机制的研究。对操作的习惯化并未影响酒精敏感和酒精不敏感大鼠品系之间原本的行为差异。对品系对酒精的运动功能损害和催眠作用的不同敏感性也没有任何影响。外周机制可能参与了这些品系的不同行为，因为酒精敏感动物的血浆皮质酮反应要弱得多，这表明它们对应激和酒精的反应能力有限。在酒精敏感大鼠的小脑中，体内对苯二氮䓬拮抗剂[³H]Ro 15 - 1788的摄取也发现了对急性乙醇暴露的类似钝化反应。这些大鼠品系在其脑抑制性GABA能受体方面没有任何一般差异的发现扩展到了脊髓抑制性甘氨酸能受体，后者在解离常数上仅表现出适度的品系差异。两种主要受体差异（高亲和力[³H]蝇蕈醇结合和[³H]Ro 15 - 4513结合的地西泮敏感性）明显定位于小脑颗粒层，这表明酒精敏感大鼠的颗粒细胞发生了基因改变。总之，我们对中等剂量酒精急性中毒的研究表明，几种中枢神经和外周因素可能参与了这种行为。由于这些因素中的许多都减轻了酒精的作用，酒精拮抗治疗应该旨在激活和支持多种适应性现象。
