dos Santos Angela Amâncio, Pinheiro Patrícia Calado Ferreira, de Lima Denise Sandrelly Cavalcanti, Ozias Mirella Gondim, de Oliveira Manuella Batista, Guimarães Natália Xavier, Guedes Rubem Carlos Araújo
Departamento de Nutrição, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil.
Exp Neurol. 2006 Aug;200(2):275-82. doi: 10.1016/j.expneurol.2006.02.014. Epub 2006 Apr 17.
Wistar rats (n = 58) were injected subcutaneously during the lactation period with fluoxetine (5, 10, 20 or 40 mg/kg/day) and cortical spreading depression (SD) was recorded immediately after weaning (25-30 days of life). An additional group (10 mg/kg; n = 8) was SD-recorded at 60-70 days. As compared to the saline-injected (n = 24) or "ingenuous" (n = 16) controls, fluoxetine dose-dependently reduced (P < 0.05) SD-velocities in the young rats by 4, 6, 16 and 15%, respectively, and in adult rats by 13%. In another experiment (26 adult rats), topical cortical application of fluoxetine (5 and 10 mg/ml solutions over the intact dura-mater for 10 min; n = 12 and 14, respectively) dose-dependently reduced SD-velocity (7.6% and 43.3% maximal reductions; P < 0.05). SD-propagation was blocked in 4 out of the 14 W-rats topically treated with the highest fluoxetine concentration (10 mg/ml). This topical fluoxetine effect was reverted after flushing the treated region with saline. In additional, 58 early-malnourished rats, fluoxetine applied during the suckling period (10 mg/kg/day, s.c.) and topically (10 mg/ml) also reduced (P < 0.05) SD-velocities by 18 and 22% for the systemic treatment (young and adult animals, respectively) and by 22.4% for the topical one. The present fluoxetine action supports the hypothesis of an antagonistic serotoninergic influence on SD, as previously suggested in experiments using other serotoninergic drugs. Data also suggest that early malnutrition does not greatly affect fluoxetine effects on SD.
在哺乳期，对58只Wistar大鼠皮下注射氟西汀（5、10、20或40毫克/千克/天），并在断奶后（出生25 - 30天）立即记录皮层扩散性抑制（SD）。另外一组（10毫克/千克；n = 8）在60 - 70天记录SD。与注射生理盐水的对照组（n = 24）或“正常”对照组（n = 16）相比，氟西汀使幼鼠的SD速度剂量依赖性降低（P < 0.05），分别降低了4%、6%、16%和15%，成年大鼠降低了13%。在另一项实验中（26只成年大鼠），在完整硬脑膜上局部应用氟西汀（5和10毫克/毫升溶液，持续10分钟；分别为n = 12和14），剂量依赖性降低了SD速度（最大降低7.6%和43.3%；P < 并在14只局部用最高氟西汀浓度（10毫克/毫升）处理的W大鼠中有4只阻断了SD传播。用生理盐水冲洗处理区域后，这种局部氟西汀效应得以逆转。此外，对58只早期营养不良的大鼠，在哺乳期全身应用氟西汀（10毫克/千克/天，皮下注射）和局部应用（10毫克/毫升）也降低了（P < 0.05）SD速度，全身治疗（幼鼠和成年动物）分别降低了18%和22%，局部治疗降低了22.4%。目前氟西汀的作用支持了5）。如先前在使用其他5-羟色胺能药物的实验中所提示的，5-羟色胺能对SD有拮抗作用的假说。数据还表明，早期营养不良对氟西汀对SD的影响没有太大影响。
