Ruotsalainen S, MacDonald E, Miettinen R, Puumala T, Riekkinen P, Sirviö J
A.I. Virtanen Institute, University of Kuopio, Finland.
Psychopharmacology (Berl). 1997 Apr;130(4):303-12. doi: 10.1007/s002130050244.
The role of serotonin (5-HT) and its interaction with the muscarinic or nicotinic receptor-mediated mechanisms in the modulation of working memory and motor activity was investigated by assessing the effects of 5-HT lesion and cholinergic receptor blockade on the performance of rats in a working memory (delayed non-matching to position, DNMTP) task. A global serotonergic lesion was induced by the intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT). Post-mortem neurochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in frontal and parieto-occipital cortices and in hippocampi of 5,7-DHT lesioned rats. 5-HIAA levels were also reduced in striatum. 5,7-DHT lesion slightly impaired choice accuracy of rats in the DNMTP task and also transiently reduced motor activity in rats. Even the lower dose of scopolamine (0.075 mg/kg), a muscarinic receptor antagonist, impaired the choice accuracy already at the shortest delay (i.e. not indicative of a working memory impairment per se), and caused a marked disruption of motor activity (lengthened response latencies, increased probability of omissions and decreased trials completed). Furthermore, the quaternary analogue, N-methylscopolamine (0.150 mg/kg), affected the motor activity of rats to the same extent as scopolamine. Mecamylamine (1.0; 3.0 mg/kg) also interfered with motor activity and it slightly decreased the choice accuracy, which was not dependent on the delay. Although mecamylamine disrupted the performance of rats in the DNMTP task, the disruption was not as severe as that seen with scopolamine. Moreover, both scopolamine and mecamylamine augmented the slight impairment on the choice accuracy of 5,7-DHT lesioned rats, but this was non-mnemonic in character. We conclude that there is no evidence for any major interaction between the serotonergic system and muscarinic or nicotinic cholinergic mechanisms in working memory per se, but muscarinic and nicotinic receptor antagonists may act additively with the 5,7-DHT lesion to disrupt the choice accuracy of rats.
通过评估5-羟色胺（5-HT）损伤和胆碱能受体阻断对大鼠在工作记忆任务（延迟位置不匹配，DNMTP）中的表现的影响，研究了5-HT及其与毒蕈碱或烟碱受体介导机制在调节工作记忆和运动活动中的相互作用。通过脑室内注射5,7-二羟基色胺（5,7-DHT）诱导整体5-羟色胺能损伤。死后神经化学分析显示，5,7-DHT损伤大鼠的额叶和顶枕叶皮质以及海马中的5-羟色胺和5-羟吲哚乙酸（5-HIAA）水平降低。纹状体中的5-HIAA水平也降低。5,7-DHT损伤轻微损害了大鼠在DNMTP任务中的选择准确性，并且还短暂降低了大鼠的运动活动。即使是较低剂量的东莨菪碱（0.075mg/kg），一种毒蕈碱受体拮抗剂，在最短延迟时就已经损害了选择准确性（即本身并不表明工作记忆受损），并导致运动活动的明显破坏（反应潜伏期延长、遗漏概率增加和完成试验减少）。此外，季铵类似物N-甲基东莨菪碱（0.150mg/kg）对大鼠运动活动的影响与东莨菪碱相同。美加明（1.0；3.0mg/kg）也干扰运动活动，并略微降低选择准确性，这与延迟无关。尽管美加明破坏了大鼠在DNMTP任务中的表现，但这种破坏不如东莨菪碱严重。此外，东莨菪碱和美加明都加剧了5,7-DHT损伤大鼠在选择准确性上的轻微损害，但这在性质上并非记忆性的。我们得出结论，没有证据表明5-羟色胺能系统与毒蕈碱或烟碱胆碱能机制在工作记忆本身中有任何主要相互作用，但毒蕈碱和烟碱受体拮抗剂可能与5,7-DHT损伤相加作用，破坏大鼠的选择准确性。
