Andreassen O A, Finsen B, Ostergaard K, Sørensen J C, West M J, Jørgensen H A
Department of Physiology, University of Bergen, Norway.
Neuroscience. 1999 Jan;88(1):27-35. doi: 10.1016/s0306-4522(98)00175-4.
Neuroleptic-induced oral dyskinesias in rats, a putative analogue to human tardive dyskinesia, may be due to excitotoxic degeneration within the striatum. Haloperidol treatment for 34 weeks increased the optical density of preproenkephalin messenger RNA in individual striatal neurons and enkephalin peptide in the neuropil, regardless of the level of oral dyskinesia produced. However, using unbiased stereological methods, an increased number of striatal neurons expressing preproenkephalin messenger RNA was observed only in rats that did not develop pronounced oral dyskinesias during haloperidol treatment. Said in another manner, the haloperidol-treated animals that developed pronounced oral dyskinesias, failed to produce an increase in the number of neurons expressing preproenkephalin messenger RNA. These results indicate that the mechanism by which neuroleptics induce oral dyskinesias in rats, and perhaps tardive dyskinesia in humans, involves a functional disturbance or even damage to a subpopulation of enkephalinergic neurons in the striatum.
大鼠中由抗精神病药物诱发的口部运动障碍，被认为是人类迟发性运动障碍的类似情况，可能是由于纹状体内的兴奋性毒性变性所致。给予氟哌啶醇治疗34周后，无论所产生的口部运动障碍程度如何，单个纹状体神经元中的前脑啡肽原信使核糖核酸以及神经毡中的脑啡肽的光密度均会增加。然而，运用无偏倚的立体学方法，仅在氟哌啶醇治疗期间未出现明显口部运动障碍的大鼠中观察到表达前脑啡肽原信使核糖核酸的纹状体神经元数量增加。换句话说，出现明显口部运动障碍的经氟哌啶醇治疗的动物，其表达前脑啡肽原信使核糖核酸的神经元数量并未增加。这些结果表明，抗精神病药物在大鼠中诱发口部运动障碍，以及可能在人类中诱发迟发性运动障碍的机制，涉及纹状体内脑啡肽能神经元亚群的功能紊乱甚至损伤。
