Consolo S, Salmoiraghi P, Amoroso D, Kolasa K
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Neurochem. 1990 Feb;54(2):571-7. doi: 10.1111/j.1471-4159.1990.tb01909.x.
Interruption of the corticostriatal pathway by undercutting the frontal cortex resulted after 2 weeks in a 40% reduction of basal acetylcholine (ACh) release in vivo, and in inhibition of the striatal sodium-dependent high-affinity uptake of choline (SDHACU) to the same extent. The lesion, too, completely prevented the rise (about 35%) in striatal ACh content induced by oxotremorine and apomorphine acting at muscarine and dopamine receptors, respectively. Acute intraperitoneal injections of 100 mg/kg of either oxiracetam or choline chloride resulted in time-dependent recovery of ACh output from the striata of decorticated rats to control levels. Oxiracetam also normalized the ex vivo striatal SDHACU activity of decorticated rats 2 h after administration without any effect in sham-operated rats. Oxiracetam or choline chloride administered before oxotremorine (0.8 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.) reinstated the ACh-increasing effect of these agonists. It is suggested that choline chloride acts directly simply by being the precursor for ACh, whereas oxiracetam may act indirectly, possibly by increasing the availability of choline chloride for ACh synthesis. Furthermore, the frontally decorticated rat could constitute a useful model for studying means to restore the deficit in striatal cholinergic neurotransmission.
通过切断额叶皮质来中断皮质纹状体通路，两周后导致体内基础乙酰胆碱（ACh）释放减少40%，并使纹状体中胆碱的钠依赖性高亲和力摄取（SDHACU）受到同等程度的抑制。该损伤还完全阻止了由分别作用于毒蕈碱和多巴胺受体的氧化震颤素和阿扑吗啡诱导的纹状体ACh含量升高（约35%）。急性腹腔注射100mg/kg的奥拉西坦或氯化胆碱可使去皮质大鼠纹状体的ACh输出随时间恢复到对照水平。奥拉西坦在给药2小时后还使去皮质大鼠离体纹状体的SDHACU活性恢复正常，而对假手术大鼠没有任何影响。在氧化震颤素（0.8mg/kg，腹腔注射）或阿扑吗啡（1mg/kg，腹腔注射）之前给予奥拉西坦或氯化胆碱可恢复这些激动剂的ACh增加效应。提示氯化胆碱仅作为ACh的前体直接起作用，而奥拉西坦可能通过增加用于ACh合成的氯化胆碱的可用性间接起作用。此外，额叶去皮质大鼠可能构成一个有用的模型，用于研究恢复纹状体胆碱能神经传递缺陷的方法。
