Enginar N, Yamantürk P, Nurten A, Nurten R, Koyuncuoğlu H
Department of Pharmacology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul 34390, Turkey.
Neuropharmacology. 2003 Feb;44(2):199-205. doi: 10.1016/s0028-3908(02)00365-9.
The present study was performed to evaluate the role(s) of hypoglycemia, changes in [(3)H]glutamate binding kinetics and dopaminergic activity in the occurrence of scopolamine-induced convulsions in fasted mice after food intake. Plasma glucose levels and density (B(max)) and affinity (K(d)) of [(3)H]glutamate binding sites in whole brain synaptic membranes were determined in animals fed ad lib or fasted for 48 h and treated intraperitoneally (i.p.) with 3 mg/kg scopolamine or saline and allowed to eat for 5 min. Fasting for 48 h decreased plasma glucose levels. After refeeding, plasma glucose concentrations increased in saline treated animals, but remained unchanged in scopolamine treated animals which consumed less food. Fasting for 48 h also produced significant changes in the kinetics of [(3)H]glutamate binding. The B(max) and K(d) of the binding sites decreased in fasted animals. These changes were partially antagonized by scopolamine treatment and food intake. For the evaluation of the contribution of dopaminergic activity, another group of mice fasted for 48 h and pretreated (i.p.) with saline or dopamine antagonists, 2 mg/kg chlorpromazine or 2 or 4 mg/kg haloperidol, were treated 10 min later with either saline or 3 mg/kg scopolamine. Then 20 min later, they were allowed to eat ad lib and were observed for 30 min for the incidence and onset of clonic convulsions. Pretreatment of both 2 mg/kg chlorpromazine and 4 mg/kg haloperidol markedly suppressed the convulsions. These results indicate that the decrease in the [(3)H]glutamate binding induced by fasting, its antagonism by scopolamine treatment and food intake, and the dopaminergic hyperactivity may be possible factors contributing to the occurrence of convulsions.
本研究旨在评估低血糖、[³H]谷氨酸结合动力学变化及多巴胺能活性在禁食小鼠进食后东莨菪碱诱导惊厥发生中的作用。测定随意进食或禁食48小时的动物全脑突触膜中[³H]谷氨酸结合位点的血浆葡萄糖水平、密度（Bmax）和亲和力（Kd），这些动物腹腔注射（i.p.）3mg/kg东莨菪碱或生理盐水，并允许进食5分钟。禁食48小时会降低血浆葡萄糖水平。重新进食后，生理盐水处理的动物血浆葡萄糖浓度升高，但在进食较少的东莨菪碱处理动物中保持不变。禁食48小时还会使[³H]谷氨酸结合动力学发生显著变化。禁食动物中结合位点的Bmax和Kd降低。这些变化部分被东莨菪碱处理和进食所拮抗。为评估多巴胺能活性的作用，另一组禁食48小时并预先腹腔注射生理盐水或多巴胺拮抗剂（2mg/kg氯丙嗪或2或4mg/kg氟哌啶醇）的小鼠，10分钟后分别用生理盐水或3mg/kg东莨菪碱处理。然后20分钟后，让它们随意进食，并观察30分钟，记录阵挛性惊厥的发生率和发作情况。2mg/kg氯丙嗪和4mg/kg氟哌啶醇预处理均显著抑制惊厥。这些结果表明，禁食诱导的[³H]谷氨酸结合减少、东莨菪碱处理和进食对其的拮抗作用以及多巴胺能亢进可能是导致惊厥发生的潜在因素。
