Neuroprotective effect of chronic verapamil treatment on cognitive and noncognitive deficits in an experimental alzheimer's disease in rats

Abstract

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.

Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance

“…E3 mice subjected to dietary challenge displayed an increase in aggression at a level similar to that of E4 mice, while -/-mice did not display any increase (Table 1). This differential impact is consistent with prior studies indicating that cognitive performance can be improved in rodents independently of aggression [57,58]. Similarly, while both cognitive impairment and aggression accompany AD, they are not necessarily temporally colocalized and may but do not necessarily respond to identical treatments [59][60][61][62].…”

Calcium channel blockers and dementia

“…Selective blockade of the N-type calcium channel by ziconotide (Berman et al, 2000;Verweij et al, 2000) and blockade of L-type calcium channels by verapamil (Hosaka et al, 1991) also protected neurodegeneration, indicating that blockade of both pre-and postsynaptic calcium influxes could be neuroprotective. In a nucleus basalis lesion model in rats, which mimics the cholinergic degeneration in AD, verapamil prevented behavioural deficits that occur as a result of the lesion (Popović et al, 1997). Blocking calcium-activated proteases further downstream prevented Aβ oligomer-induced nucleus basalis lesions, degeneration of cholinergic fibres as well as associated behavioural deficits (Granic et al, 2010).…”

A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents

“…The two nondihydropyridine CCBs that have been studied in the context of AD are verapamil and diltiazem. Both ameliorate neurotoxicity caused by Aβ and verapamil may also reduce Aβ(1–40) oligomer levels (table 4) [45,97,98]. …”