Lewis S J, Quinn M J, Fennessy M R, Jarrott B
Clinical Pharmacology and Therapeutics Unit, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Pharmacol Biochem Behav. 1989 May;33(1):75-9. doi: 10.1016/0091-3057(89)90432-2.
The intracerebroventricular (ICV) injection of the mast cell degranulator Compound 48/80 (2.5-2.0 micrograms/kg) produced a marked behavioral syndrome in normotensive rats. The behaviors included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, and a later phase of sedation. The highest doses (15 and 20 micrograms/kg) also produced catalepsy and episodes of "barrel rolling" (continuous rolling of 1-8 turns around the longitudinal axis). These behaviors were observed for approximately 15-30 min although the sedation and catalepsy were maintained for 90-120 min. A second ICV injection of the 10 micrograms/kg dose of Compound 48/80 given 2 hr after an initial injection of this dose, produced a much reduced response and the numbers of head and body shakes, and episodes of paw tremor and grooming were between 20-30% of those produced by the first injection. The reduced effect of the second injection indicates that the behavioral effects of Compound 48/80 may arise from the acute degranulation of mast cells rather than direct effects on neuronal populations or the cerebral vasculature.
向正常血压大鼠脑室内(ICV)注射肥大细胞脱颗粒剂化合物48/80(2.5 - 2.0微克/千克)会引发明显的行为综合征。这些行为包括头部和身体颤抖、爪部震颤、过度梳理毛发、异常姿势和步态、轻度腹泻、竖毛、极度激动以及对触摸敏感,随后进入镇静期。最高剂量(15和20微克/千克)还会导致僵住症和“翻滚”发作(围绕纵轴连续翻滚1 - 8圈)。这些行为持续约15 - 30分钟,不过镇静和僵住症会持续90 - 120分钟。在首次注射10微克/千克剂量的化合物48/80两小时后,再次进行脑室内注射,产生的反应明显减弱,头部和身体颤抖的次数以及爪部震颤和梳理毛发的发作次数仅为首次注射时的20% - 30%。第二次注射效果减弱表明,化合物48/80的行为效应可能源于肥大细胞的急性脱颗粒,而非对神经元群体或脑血管系统的直接作用。