Popović M, Caballero-Bleda M, Popović N, Bokonjić D, Dobrić S
Departamento de Ciencias Morfologicas y Psicobiologia, Facultad de Medicina, Universidad de Murcia, Spain.
Int J Neurosci. 1997 Nov;92(1-2):79-93. doi: 10.3109/00207459708986392.
It is well known that disturbance of calcium homeostasis has a significant role in the development of neurodegenerative disorders, such as Alzheimer's disease (AD). Our recent data suggest that acute treatment with the calcium antagonist verapamil can improve some behavioral deficits in an experimental model of AD. Therefore, the present study was done to establish the effect of chronically administered verapamil on cognitive and noncognitive behavior of rats with bilateral electrolitical lesions of nucleus basalis manocellularis (NBM)--an animal model of AD. The NBM lesions produce a deficit in performance of diverse behavior tests: active avoidance (AA), low level of fear (the open field test) as well as aggressive (the test of foot-shock induced aggression) and depressive (the learned helplessness test) behavior. Verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg i.p.) or saline solution (1 ml/kg i.p.) were injected 24 hr after the lesion of NBM and then repeatedly administered during the next 8 days (twice a day). Performance of the two-way active avoidance test, the open field test, the foot shock-induced aggression test and the learned helplessness test were done on day 4 after the last verapamil or saline treatment (day 13 after the lesion). Verapamil in doses of 2.5 and 5.0 mg/kg significantly ameliorated the deficit in the performance of AA, the open field behavior, and the depression, but not the aggressive behavior. The obtained beneficial effect of chronic administered verapamil suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a reasonable way to prevent the behavioral deficits in an experimental model of AD.
众所周知，钙稳态紊乱在神经退行性疾病（如阿尔茨海默病，AD）的发展中起着重要作用。我们最近的数据表明，用钙拮抗剂维拉帕米进行急性治疗可以改善AD实验模型中的一些行为缺陷。因此，本研究旨在确定长期给予维拉帕米对基底核单细胞部（NBM）双侧电解损伤大鼠（一种AD动物模型）的认知和非认知行为的影响。NBM损伤会导致多种行为测试表现出现缺陷：主动回避（AA）、低恐惧水平（旷场试验）以及攻击性行为（足部电击诱发攻击试验）和抑郁行为（习得性无助试验）。在NBM损伤后24小时注射维拉帕米（1.0、2.5、5.0和10.0mg/kg腹腔注射）或生理盐水溶液（1ml/kg腹腔注射），然后在接下来的8天内重复给药（每天两次）。在最后一次维拉帕米或生理盐水治疗后的第4天（损伤后第13天）进行双向主动回避试验、旷场试验、足部电击诱发攻击试验和习得性无助试验。2.5和5.0mg/kg剂量的维拉帕米显著改善了AA表现、旷场行为和抑郁方面的缺陷，但对攻击性行为没有改善作用。长期给予维拉帕米所获得的有益效果表明，在NBM损伤后的早期调节钙稳态可能是预防AD实验模型中行为缺陷的一种合理方法。
