Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…Additionally, in line with the hypothesis that oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer's disease, both donepezil and tacrine suppressed STZ-icv-induced oxidative stress by normalizing decreased glutathione (GSH) and increased malondialdehyde (MDA) levels (Saxena et al 2008). Mice treated with 0.1 mg/kg i.p.…”

“…These effects were achieved regardless of whether the treatment began 1 week prior to, in parallel, or 13 days after the STZ-icv administration. In another experiment on mice treated STZ-icv with a 1 mg/kg dose who developed severe cognitive deficits 14 days after the STZ-icv administration, oral treatment with donepezil or tacrine (5 mg/kg both) one hour prior to the memory testing in Passive avoidance and Morris Water Maze tests, caused a significant improvement of the memory impairment, associated with a significant decrease in AChE activity (Saxena et al 2008). …”

Scopolamine-induced learning impairment reversed by physostigmine in zebrafish

“…By way of contrast, muscarinic receptor agonists such as pilocarpine have been demonstrated to reduce scopolamine-induced impairments in avoidance response (De-Mello et al, 2005). AChE inhibitors such as rivastigmine, donepezil, and galantamine are all used to improve memory deficits in humans and animals (Saxena et al, 2008;Benetti et al, 2009;Pepeu and Giovannini, 2009). The inhibition of acetylcholinesterase (AChE) which breaks acetylcholine down into acetyl CoA and choline, increases acetylcholine levels in the synaptic cleft, and thus enhances cholinergic transmission, which leads to improvements in learning and cognitive deficits.…”

The inhibitory avoidance test optimized for discovery of cognitive enhancers

“…These two distributions were partially overlapping in the single-trial acquisition protocol. We also demonstrated that the double-trial acquisition protocol was particularly sensitive to well-known acetylcholinesterase inhibitors such as tacrine and donepezil-drugs with demonstrated efficacy against scopolamine in this test (Dawson & Iversen, 1993;Pan et al, 2006;Saxena, Singh, Agrawal, & Nath, 2008;Shutske et al, 1989). Finally, we provided evidence about the reproducibility of the behavioral performance over a period of 3 years, showing reproducible scopolamine-induced long-term-memory impairments and the prevention of such a deficit by tacrine.…”