Peterson S L, Armstrong J J
College of Pharmacy, University of New Mexico, Albuquerque 87131, USA.
Epilepsia. 1999 Jan;40(1):20-5. doi: 10.1111/j.1528-1157.1999.tb01983.x.
Previous reports from this laboratory indicated a role for N-methyl-D-aspartic acid (NMDA) and gamma-aminobutyric acid (GABA) receptors among the neuronal mechanisms of the nucleus reticularis pontis oralis (RPO) that regulate the tonic hindlimb extension (THE) component of maximal electroshock seizures (MESs) in rats. This study was intended to determine the role of cholinergic mechanisms in the RPO regulation of THE.
Rats were surgically prepared with microinjection guide cannulas for the focal administration of drug solutions directly into the RPO. MES was induced with corneal electrodes.
RPO microinjection of carbachol significantly inhibited the incidence of THE. RPO microinjection of atropine by itself had no effect on the seizure response but significantly antagonized the anticonvulsant effect induced by RPO microinjection of carbachol. The selective nicotinic agonist dimethylpiperizinium (DMPP) by itself had no effect on THE. RPO microinjection of 10 ng pertussis toxin by itself had no effect on THE but significantly antagonized the anticonvulsant effect induced by RPO microinjection of carbachol.
RPO microinjection of carbachol inhibited the THE component of MESs in rats. The carbachol effect appeared to be mediated by muscarinic receptors as the anticonvulsant activity was antagonized by atropine, and the selective nicotinic agonist DMPP induced no anticonvulsant activity. Because pertussis toxin acts to inhibit muscarinic receptor-linked G proteins, the pertussis toxin antagonism of carbachol also supports a muscarinic mechanism of action.
本实验室之前的报告表明，在大鼠最大电休克惊厥（MES）的紧张性后肢伸展（THE）成分的调节中，N-甲基-D-天冬氨酸（NMDA）和γ-氨基丁酸（GABA）受体在脑桥嘴侧网状核（RPO）的神经元机制中发挥作用。本研究旨在确定胆碱能机制在RPO对THE的调节中的作用。
通过手术给大鼠制备显微注射引导套管，以便将药物溶液直接局部注射到RPO中。用角膜电极诱发MES。
向RPO显微注射卡巴胆碱可显著抑制THE的发生率。单独向RPO显微注射阿托品对惊厥反应无影响，但可显著拮抗向RPO显微注射卡巴胆碱所诱导的抗惊厥作用。选择性烟碱激动剂二甲基哌嗪鎓（DMPP）单独使用对THE无影响。单独向RPO显微注射10 ng百日咳毒素对THE无影响，但可显著拮抗向RPO显微注射卡巴胆碱所诱导的抗惊厥作用。
向RPO显微注射卡巴胆碱可抑制大鼠MES的THE成分。卡巴胆碱的作用似乎是由毒蕈碱受体介导的，因为抗惊厥活性被阿托品拮抗，且选择性烟碱激动剂DMPP未诱导出抗惊厥活性。由于百日咳毒素可抑制与毒蕈碱受体相关的G蛋白，百日咳毒素对卡巴胆碱的拮抗作用也支持其毒蕈碱作用机制。
